InteractiveFly: GeneBrief

Grasp65: Biological Overview | References

Gene name - Grasp65

Synonyms -

Cytological map position - 76D5-76D5

Function - signaling

Keywords - acquisition of Golgi stack morphology

Symbol - Grasp65

FlyBase ID: FBgn0036919

Genetic map position - 3L: 19,918,160..19,919,979 [+]

Classification - GRASP55/65 family

Cellular location - cytoplasmic

NCBI link: EntrezGene

Grasp65 orthologs: Biolitmine

The de novo model for Golgi stack biogenesis predicts that membrane exiting the ER at transitional ER (tER) sites contains and recruits all the necessary molecules to form a Golgi stack, including the Golgi matrix proteins, p115, GM130, and the Golgi ReAssembly Stacking Protein GRASP65/55 (Barr, 1997). GRASP65 is part of a complex at cis-Golgi membranes with the golgin GM130 that acts as a receptor for the vesicle tethering factor p115. These three proteins leave the tER sites faster than Golgi transmembrane resident enzymes, suggesting that they act as a template nucleating the formation of the Golgi apparatus. However, the localization of the Golgi matrix proteins at tER sites is shown only under conditions where exit from the ER is blocked. This study shows, in Drosophila S2 cells, that dGRASP, the single Drosophila homologue of GRASP65/55, localizes both to the Golgi membranes and the tER sites at steady state and that the myristoylation of glycine 2 is essential for the localization to both compartments. Its depletion for 96 h by RNAi gave an effect on the architecture of the Golgi stacks in 30% of the cells, but a double depletion of dGRASP and dGM130 led to the quantitative conversion of Golgi stacks into clusters of vesicles and tubules, often featuring single cisternae. This disruption of Golgi architecture was not accompanied by the disorganization of tER sites or the inhibition of anterograde transport. This shows that, at least in Drosophila, the structural integrity of the Golgi stacks is not required for efficient transport. Overall, dGRASP exhibits a dynamic association to the membrane of the early exocytic pathway and is involved in Golgi stack architecture (Kondylis, 2005).

The Golgi apparatus has a unique and almost universal membrane architecture. Its basic component, the flattened membrane bound compartment called cisterna, is found in almost all eukaryotic species with the exception of some primitive protists. In most eukaryotes, cisternae are arranged in a parallel manner to form a stack, on each side of which is found one tubular-vesicular network, the cis- and trans-Golgi network (Kondylis, 2005).

Two opposing models have been proposed to explain the biogenesis of this unique organelle, the Golgi matrix model and the de novo Golgi formation model. According to the first, the Golgi apparatus is an autonomous organelle built on a preexisting template, as suggested by data from a variety of organisms. For instance, microsurgically created peripheral cytoplasts from mammalian cells that do no longer contain any Golgi membrane failed to produce a Golgi apparatus, although they contained a significant amount of ER membranes (Pelletier, 2000). Furthermore, studies on the Golgi stack duplication in two protozoa have provided support to a template-mediated mechanism of Golgi formation, both in Trypanosoma brucei (He, 2004) and Toxoplasma gondii (Pelletier, 2002; Kondylis, 2005 and references therein).

In mammalian cells, the template is proposed to be a Golgi matrix (Slusarewicz, 1994; Shorter, 2002) formed by Golgi matrix proteins, which comprise golgins, a group of long coiled-coil proteins localizing in the Golgi membranes, such as p115 and GM130, and the Golgi reassembly and stacking proteins GRASP65 and GRASP55 (Barr, 2003). All these proteins have been implicated in the building and/or maintenance of the Golgi stack architecture, and the role of p115 in the structural integrity of the Golgi apparatus is the best established (Kondylis, 2005 and references therein).

GRASP65 and GRASP55 were originally identified as cisternal stacking factors (Barr, 1997; Shorter, 1999) and were shown to act as Golgi receptors for GM130 and golgin45, respectively (Barr, 1998; Short, 2001). GRASP65 is anchored on the Golgi membranes by myristoylation of the glycine residue at position 2 (Barr, 1997) and forms dimers that could directly stack neighboring cisternae by forming transoligomers (Shorter, 1999; Wang, 2003; Wang, 2005). This oligomerization is mediated by the N-terminal GRASP domain and is regulated by phosphorylation of serine/threonine residues at the C-terminal half of the protein during mitosis (Preisinger, 2005; Wang, 2005; Kondylis, 2005 and references therein).

In addition, several recent studies have suggested that GRASP65 is also crucial for cell cycle regulation (Sutterlin, 2002; Preisinger, 2005), apoptosis (Lane, 2002), and growth (Yoshimura, 2005). Regarding this latter role, the mitotically Cdk1-phosphorylated serine 277 of GRASP65 is also phosphorylated in interphase by ERK kinase, and this is enhanced by the addition of epidermal growth factor (EGF) (Preisinger, 2005; Yoshimura, 2005; Kondylis, 2005 and references therein).

The second model of Golgi stack biogenesis, the de novo Golgi formation, considers the Golgi apparatus as an outgrowth of ER exit sites or transitional ER (tER) sites, the specialized ER subdomains where cargo proteins destined for the Golgi apparatus are packaged into COPII-coated vesicles. This model proposes that the membranes exiting the tER sites contain all the necessary molecular information to trigger the building of a functional Golgi apparatus by a mechanism of self-organization. This model has been supported by experimental observations on GRASP65. First, live cell imaging studies of GFP-tagged GRASP65 have shown that it exhibits a dynamic association on and off the Golgi membranes (Marra, 2001; Ward, 2001). Second, using either reagents that block ER-to-Golgi transport, such as Sar1p and Arf1 mutants, or the drugs brefeldin A and H89, GRASP65 was reported to undergo cycling between the Golgi apparatus and the ER exit sites, similar to other golgins. Overall, these results have been taken as evidence that GRASP proteins along with other Golgi matrix proteins could be recruited to the membranes exiting the tER sites and differentiate them into a Golgi apparatus (Glick, 2002; Altan-Bonnet, 2004; Kondylis, 2005 and references therein).

These two models have recently been reconciled to propose that the biogenesis of the Golgi apparatus occurs through a self-organizing nucleation mechanism. GM130, GRASP65, and GRASP55 were shown to leave the tER sites faster than the Golgi enzymes upon removal of ER exit blocks (Puri, 2003; Kasap, 2004), suggesting that Golgi matrix proteins could be able to form a template facilitating the acquisition of Golgi stack morphology (Kondylis, 2005).

In Drosophila, Golgi stacks exhibit a close spatial association with tER sites, forming tER-Golgi units (Kondylis, 2003; Herpers, 2004), comparable to those observed in Pichia (Rossanese, 1999; Mogelsvang, 2003), Trypanosoma (He, 2004), and plants (DaSilva, 2004; Kondylis, 2005 and references therein).

This study shows that the single Drosophila GRASP homologue, dGRASP, exhibits a steady state localization to both the Golgi membranes and the tER sites under normal growth conditions in Drosophila cells and tissues. When depleted from S2 cells by RNAi, alone or in combination with dGM130, the fly homologue of GM130, the Golgi stack architecture is quantitatively disrupted into Golgi clusters, as suggested from its role in mammalian cells. However, the tER organization remains unaffected, as well as the anterograde transport from the ER to the plasma membrane through the Golgi clusters. This suggests that Golgi stack integrity is not necessary for anterograde transport (Kondylis, 2005).

The exocytic pathway in Drosophila S2 cells is organized as ~20 tER-Golgi units (Kondylis, 2003), located throughout the cytoplasm, made of a Golgi apparatus in very close proximity to one tER site. The Drosophila Golgi stacks exhibit the same basic features as the mammalian ones (e.g., the polarity, the number of cisternae per stack), though their cross-sectional diameter is significantly smaller (with an average of 368 nm in S2 cells). The tER sites, marked by dSec23p (a GTPase-activating protein and a component of the Sec23p-Sec24p heterodimeric complex of the COPII vesicle coat, involved in ER to Golgi transport and autophagy), also exhibit similar morphological features, though they appear significantly larger than in mammalian cells (Kondylis, 2005).

Anterograde transport of cargo takes place similarly in mammalian and Drosophila tissue culture cells, both being sensitive to BFA, H89 and the depletion of syntaxin 5/dSed5p Moreover, both drugs have similar effects on the Golgi resident proteins and the tER site organization. Drosophila S2 cells are therefore an excellent biological system to investigate issues related to membrane traffic and organelle architecture. The simplified but comparable organization of their exocytic pathway provides the possibility to examine the molecular mechanisms underlying both its structure and functions (Kondylis, 2005).

Because of the action of the golgi vesicle-tethering factor dp115, dGRASP localizes both to the tER sites and the Golgi apparatus. dGRASP localizes throughout the Golgi stack and peripheral Golgi elements, similar to the mammalian GRASPs (Shorter, 1999). dGRASP was also observed between cisternae, and when S2 cells were depleted of this protein, a small but significant percentage exhibited a single cisterna phenotype, which is consistent with the in vivo and in vitro role of GRASP65 and GRASP55 in cisternal stacking (Barr, 1997; Shorter, 1999; Wang, 2003; Kondylis, 2005 and references therein).

In addition to single cisternae, the depletion of dGRASP also led to the conversion of Golgi stacks into clusters of vesicles and tubules. This could be due to the fact that single cisternae are relatively unstable and break down easily. Alternatively, dGRASP could be involved in the formation of Golgi cisternae. Independently of the mechanism, this phenotype was strengthened by the double depletion of dGRASP together with Golgi-matrix protein dGM130. The stronger phenotype observed when the two proteins are depleted together than when either one is depleted alone could be interpreted as a genetic interaction. Because in mammalian cells GM130 interacts biochemically with GRASP65 (Barr, 1998), it was hypothesized that the observed genetic interaction in S2 cells could also reflect a biochemical one, but this would need to be confirmed (Kondylis, 2005).

Although RNAi results in S2 cells have confirmed a role of dGRASP in Golgi architecture, this function is unlikely to be the only one in the exocytic pathway. First, a GRASP-like homologue is present in the genome of Encephalitozoon cuniculi, a protist containing the smallest eukaryotic genome sequenced to date, which does not exhibit a typical stacked Golgi apparatus. Second, dGRASP also localized on the tER sites. The myristoylation of the glycine at position 2 is required for this localization (as well as for the Golgi), because its mutation to an alanine abolishes most of its membrane association. This does not exclude that other dGRASP domains could be also necessary. dGRASP myristoylation is only mediating the association with tER and Golgi membranes and additional, yet unidentified, proteins and/or lipids are also likely to be the determinants for this localization (Kondylis, 2005).

Despite its localization on tER membranes, dGRASP depletion (alone or in combination with dGM130) did not lead to any disorganization of the tER sites, as assessed by immunofluorescence or IEM, contrary to what has been reported for dp115 depletion (Kondylis, 2003; Kondylis, 2005).

dGRASP could give the membranes exiting the tER sites their Golgi identity, as suggested by the self-organizing nucleation mechanism proposed to explain the Golgi stack formation (Kasap, 2004). Except for dp115, dGRASP is the only example thus far of a Golgi matrix protein being localized at the tER sites under normal steady state conditions, whereas in mammalian cells this localization has been exemplified only under conditions of ER exit block. This suggests that dGRASP could cycle between tER sites and Golgi stack faster or more than its mammalian homologues. dGRASP could be first recruited to the Golgi stack and then cycles very rapidly back to the tER sites or first recruited to the tER sites and delivered to the Golgi apparatus upon anterograde transport. The latter possibility seems perhaps unlikely, because newly synthesized GRASP65 was found associated with Golgi membranes upon an ER exit block (Yoshimura, 2001). As a final possibility, dGRASP could be dynamically recruited from the cytosol to both the tER and Golgi membranes, as suggested by the rapid recovery of fluorescence in the FRAP experiment, although this result cannot formally exclude a rapid transport between both compartments (Kondylis, 2005).

The double depletion of dGM130/dGRASP did not lead to a significant inhibition of anterograde transport, at least at steady state. Mammalian GRASP65 (and GM130) have been implicated in anterograde transport by capturing cargo-containing carriers emanating from the intermediate compartment to the cis-Golgi (Marra, 2001). Nevertheless, in Drosophila S2 cells, the role of dGRASP could be nonessential because of the short distance between the tER sites and the Golgi stack (Kondylis, 2005).

This result shows that, as for dp115 (Kondylis, 2003), Golgi stack structure is not required for efficient anterograde transport, at least in Drosophila. Of course, there are many indications in the literature for this, ranging from the secretion in budding yeast that lacks Golgi stacks to those of lower eukaryotes, such as E. cuniculi, that have no obvious Golgi stacks but contain genes encoding proteins of Golgi budding and fusion machinery, as well as some matrix proteins. The current data, however, shows that cells that normally have a stacked Golgi apparatus do not need it for transporting the bulk of proteins and so puts into sharp focus the real relationship between Golgi structure and its supposed primary function. Functional Golgi clusters have also been described in vivo in Drosophila (Kondylis, 2001). Moreover, recently, the depletion of p125 that affects the organization of the tER sites, and ultimately the Golgi structure, does not inhibit forward transport of the secretory membrane protein vesicular stomatitis virus glycoprotein (Kondylis, 2005).

That the depletion of dGRASP did not affect anterograde transport of the transmembrane protein Delta to a significant extent does not mean that the transport of specific proteins might not be affected. GRASP65 has been reported to act as a chaperone for the transport of the TGF-alpha proteins to the plasma membrane in human cells, and conversely to be part of a retention mechanism for the p24 family members to the cis-Golgi (Barr, 2001). The transport of TGF-alpha proteins (Gurken, Spitz, and Keren) has not been investigated in S2 cells. However, the retention of a member of the p24 family, p24delta1, has been invstigated, but no change was found in its distribution upon dGRASP depletion (Kondylis, 2005).

Taken together, these results indicate that dGRASP is dynamically localized to the early exocytic pathway (tER sites and Golgi apparatus) but has a role in the acquisition of Golgi stack morphology without affecting anterograde transport. Its presence at the tER sites is intriguing because it is not involved in their organization. This suggests that dGRASP could be recruited at the tER sites providing Golgi identity to the exiting membranes and promoting the formation of Golgi stacks either in a transient way or as part of a Golgi matrix, however dynamic (Glick, 2002; Kondylis, 2005).

In addition to the above mentioned roles, dGRASP could participate in signaling. The C-terminal half of dGRASP exhibits several phosphorylation sites, similar to GRASP65 and GRASP55. Very recently, GRASP65 was shown to be phosphorylated by ERK on serine 277 in interphase and this phosphorylation step is strongly enhanced by the addition of serum or EGF in the medium, suggesting that GRASP65 may play a role in growth factor signal transduction (Yoshimura, 2005). This is in line with the increasing number of signaling proteins reported to localize on the membranes of the early exocytic pathway, including the small GTPase upstream of ERK, the activated H-Ras, on the Golgi apparatus. This raises the question of their anchoring mechanism at these membranes. One may speculate that GRASP65 and dGRASP could act as scaffolds/receptors for these signaling proteins. Such a role has been shown for GM130 (Preisinger, 2004), which binds and regulates the function of YSK1, a kinase of the STE family implicated in polarized secretion during wound healing Kondylis, 2005).

GRASP65 is also heavily phosphorylated at its C-terminal part during mitosis (Wang, 2003; Wang, 2005). Interference with this C-terminal has led to a block in the entry of mammalian cells into mitosis (Sutterlin, 2002) or a delay in mitotic progression (Preisinger, 2005), and preliminary data from transient transfection of dGRASP C-terminus in S2 cells suggest that a similar role could apply to dGRASP. Analysis of dGRASP Drosophila mutants at different development stages is currently underway and will be useful to elucidate this issue (Kondylis, 2005).

dGRASP-mediated noncanonical integrin secretion is required for Drosophila epithelial remodeling

Integral plasma membrane proteins are typically transported in the secretory pathway from the endoplasmic reticulum and the Golgi complex. This study shows that at specific stages of Drosophila development corresponding to morphological changes in epithelia, apposed basolateral membranes separate slightly, allowing new plasma membrane contacts with basal extracellular matrix. At these sites, newly synthesized integrin α subunits are deposited via a mechanism that appears to bypass the Golgi. The Drosophila Golgi resident protein dGRASP localizes to these membrane domains, and in the absence of dGRASP, the integrin subunit is retained intracellularly in both follicular and wing epithelia that are found disrupted. It is proposed that this dGRASP-mediated noncanonical secretion route allows for developmental regulation of integrin function upon epithelial remodeling. It is speculated that this mechanism might be used during development as a means of targeting a specific subset of transmembrane proteins to the plasma membrane (Schotman, 2008).

This study has identified a developmentally regulated noncanonical dGRASP-dependent and dSyntaxin5-independent secretion route that displays several characteristics. (1) It is specifically built in epithelia that undergo rearrangement, such as the elongating discs and the flattening follicle cells. There, it is used by the transmembrane integrin subunit αPS1 for its transport and deposition at the open zone of contact (ZOC), the basolateral portion of the plasma membrane that was engaged in cell-cell contact and, after the morphological changes, is now facing the extracellular matrix. This deposition elicits the building of a focal adhesion that helps maintain epithelium integrity at stage 11 onward. In the absence of dGRASP, the specific deposition of αPS1 is dramatically impaired and the resulting epithelium is severely disrupted in a similar fashion as in a hypomorphic mew. (2) This pathway is insensitive to BFA and the absence of the SNARE dSyntaxin5, suggesting that it bypasses the Golgi (Schotman, 2008).

It is proposed that the building of this pathway starts with the upregulation of a subset of mRNAs encoding proteins of the Golgi, dGRASP and dGos28. These mRNAs are targeted to the open ZOC, where they elicit the de novo synthesis of the corresponding proteins that are found anchored at the plasma membrane lining the open ZOC in the follicular epithelium. This RNA pattern was also observed with a handful of other transcripts. Remaining to be answered is what triggers the upregulation and localization of the dgrasp mRNA and the other transcripts to the open ZOC in response to epithelial morphological changes and how they are moved and anchored there. As mechanical tension and integrin binding have already been shown to induce the recruitment of mRNAs to focal adhesions, integrins themselves could be the sensor for the mechanical stretching during disc elongation and the centripetal movement of the follicle cells (Schotman, 2008).

Concomitant with the targeting of dgrasp transcripts, αPS1 mRNA is also upregulated and basally concentrated. It is proposed that at stage 10B, the ER cisternae that reside near the open ZOC are actively involved in the local synthesis of αPS1. After synthesis in the ER membrane, a yet-unknown cargo receptor likely provides a very efficient exit for the newly synthesized αPS1 and prevents its diffusion through the entire ER membrane, similar to Gurken in the oocyte . From these αPS1-enriched ER cisternae, carriers would form, although their nature remains elusive. Although Sar1 localization has not been addressed, none of the COPII subunits were concentrated near the open ZOC (Schotman, 2008).

These ER-derived carriers bypass the Golgi and specifically fuse with the plasma membrane outlining the open ZOC. This membrane domain has become, at stage 10B, an acceptor compartment of an unexpectedly mixed nature, comprising plasma membrane resident proteins as well as cis-Golgi proteins dGRASP, dGM130, and dGos28 that are specifically localized there at this stage. These proteins could form a platform to which the αPS1-enriched ER-derived carriers fuse through the formation of a SNARE complex involving dGos28, and other SNAREs that have yet to be identified. dGRASP/dGM130 is likely to be involved in their tethering through oligomerization of dGRASP and promote the formation of this unusual complex. The fusion would involve the activity of the ATPase dNSF1 and its cofactor dSNAP, meaning that this system is clearly different from the Golgi-independent deposition of the transmembrane protein Ist2 from Saccharomyces cerevisiae that is Sec18/NSF independent (Schotman, 2008).

In addition to Ist2, a few proteins have already been shown to traffic directly from the ER to the plasma membrane, such as the cystic fibrosis transductance regulator in BTK cells and the simian rotavirus RRV in Caco-2 cells. Further research might reveal whether a pathway equivalent to the dGRASP-mediated pathway is involved in Golgi bypass in these cases (Schotman, 2008).

A number of mammalian factors, including Galectin, Interleukin, and Fibroblast growth factor 2, have been shown to be secreted in an unconventional manner that completely bypasses the exocytic pathway. Very recently, the Dictyostelium GRASP homolog GrhA has been shown to be involved in the unconventional secretion of the polypeptide AcbA that is predicted to harbor no signal peptide in its coding sequence (Schotman, 2008).

It is striking that both dGRASP and GrhA mediate unconventional secretion routes yet the pathways appear to be different. Unlike AcbA in Dictyostelium, αPS1 is translocated into the ER lumen using its signal peptide. In follicle cells earlier than stage 10B, αPS1 transport requires dSyntaxin5, suggesting that it travels via the typical ER-Golgi-plasma membrane transport route. There is no evidence suggesting that the signal peptide might be omitted at stage 10B and, importantly, no evidence of transmembrane proteins transported to the plasma membrane by the unconventional secretion pathway that AcbA is proposed to use (Schotman, 2008).

AcbA has been postulated to be captured from the cytosol and stored in endosomes prior to release from this compartment to the extracellular medium. In contrast, αPS1 could be made de novo and stored in an endosomal compartment (perhaps similar to Glut4 in adipocytes) localized near the open ZOC before being specifically recycled to the adjacent plasma membrane. Alternatively, the integrin could be stored in endosomes upon internalization from the plasma membrane, although the inhibition of integrin deposition to the open ZOC by protein synthesis inhibitors argues against this (Schotman, 2008).

Both trafficking events could be insensitive to BFA or to the loss of dSyntaxin5 function, and the tethering and fusion of the recycling vesicles, or even a whole endosome, could require dGRASP and the other proteins found near the open ZOC, in a similar fashion as the exocytic carriers proposed above. GrhA could have an equivalent role. However, the recycling to the plasma membrane of the mammalian integrins, like Glut4, has been shown to depend to a great extent on Rab11, and if this small GTPase is involved in αPS1 recycling, it would be expected to be fond concentrated near the open ZOC. This is not the case. The identification of αPS1-positive carriers in follicle cells will shed light on the mechanism involved in its deposition (Schotman, 2008).

In the Drosophila wing epithelia, αPS1 and αPS2 are substrates of the dGRASP-mediated pathway and the dgrasp wings exhibit blisters. However, when compared to the mew and inflated phenotype (not shown), dgrasp wings are smaller and rounder. This could be a result of the additive effect of stopping the transport of both αPS1 and αPS2. dGRASP itself could be involved in wing development, perhaps with a role in cell-cycle control. Other unidentified proteins involved in growth could use the same dGRASP-dependent pathway. It is also possible that the α subunits of integrin are involved in disc elongation, as they have been proposed to be in follicle cells (Schotman, 2008).

The intriguing question is why in the follicular epithelium, αPS1 uses an alternative pathway at stage 10B. The Golgi houses glycosylases and glycosyltransferases allowing the processing and building of complex oligosaccharides that are often required for the biological activity of glycoproteins. The Golgi bypass of αPS1 suggests that the oligosaccharide modifications carried out in this compartment are not necessary for αPS1 function at the open ZOC. Because the lack of a series of Golgi glycosylases enhances the adhesion activity of integrins, the Golgi bypass might indeed enhance or modulate integrin adhesion properties at this specific time of oocyte development. βPS is not a substrate of this noncanonical pathway. This is surprising, because α and β integrin subunits have been shown to oligomerize early in the secretory pathway, probably leading to their increased stability and efficient transport. These results suggest that the subunits are also able to travel on their own, perhaps by binding to other proteins (Schotman, 2008).

This study has shown that the integrin subunits αPS1 and αPS2 are not properly deposited in two different dgrasp mutant epithelia. The mechanism unraveled in this study could therefore also be used in other tissue remodeling events throughout Drosophila development involving adhesion. In this context, the basal adhesion of follicle cells shares many similarities with dorsal closure in embryos. The secretory process described could also apply here, and perhaps more generally in embryogenesis (Schotman, 2008).

This also gives an additional molecular handle to adhesion at the basal site that is crucially involved in the maintenance of epithelium integrity. Adhesion can be modulated by the phosphorylation of focal adhesion components leading to a change in integrin adhesive properties. In the follicular epithelium, the receptor tyrosine phosphatase Dlar genetically interacts with βPS with which it colocalizes in basal tricellular junctions in stage 7-8. There, it is involved in F-actin organization that ultimately stabilizes the epithelium. This study shows that adhesion can also be modulated at a pretranslational level by the transport (albeit noncanonical) and targeting of newly synthesized integrins to future adhesion sites (Schotman, 2008).

Taken together, it is proposed that the GRASP-mediated secretory route might be used during development as a means of targeting a specific subset of transmembrane proteins crucial for development to the plasma membrane (Schotman, 2008).


Search PubMed for articles about Drosophila Grasp65

Altan-Bonnet, N., Sougrat, R. and Lippincott-Schwartz, J. (2004). Molecular basis for Golgi maintenance and biogenesis. Curr. Opin. Cell Biol. 16: 364-372. PubMed ID: 15261668

Barr, F. A., Puype, M., Vandekerckhove, J. and Warren, G. (1997). GRASP65, a protein involved in the stacking of Golgi cisternae. Cell 91: 253-262. PubMed ID: 9346242

Barr, F. A., Nakamura, N. and Warren, G. (1998). Mapping the interaction between GRASP65 and GM130, components of a protein complex involved in the stacking of Golgi cisternae. EMBO J. 17: 3258-3268. PubMed ID: 9628863

Barr, F. A., Preisinger, C., Kopajtich, R. and Korner, R. (2001). Golgi matrix proteins interact with p24 cargo receptors and aid their efficient retention in the Golgi apparatus. J. Cell Biol. 155: 885-891. PubMed ID: 11739402

Barr, F. A. and Short, B. (2003). Golgins in the structure and dynamics of the Golgi apparatus. Curr. Opin. Cell Biol. 15: 405-413. PubMed ID: 12892780

DaSilva, L. L., Snapp, E. L., Denecke, J., Lippincott-Schwartz. J., Hawes, C. and Brandizzi, F. (2004). Endoplasmic reticulum export sites and Golgi bodies behave as single mobile secretory units in plant cells. Plant Cell 16: 1753-1771. PubMed ID: 15208385

Glick, B. S. (2002). Can the Golgi form de novo? Nat. Rev. Mol. Cell. Biol. 3: 615-619. PubMed ID: 12154372

He, C. Y., Ho, H. H., Malsam, J., Chalouni, C., West, C. M., Ullu, E., Toomre, D. and Warren, G. (2004). Golgi duplication in Trypanosoma brucei. J. Cell Biol. 165: 313-321. PubMed ID: 15138289

Herpers, B. and Rabouille, C. (2004). mRNA Localization and protein sorting mechanisms dictates the usage of tER-Golgi units involved in Gurken transport in Drosophila oocytes. Mol. Biol. Cell 15: 5306-5317. PubMed ID: 15385627

Kasap, M., Thomas, S., Danaher, E., Holton, V., Jiang, S. and Storrie, B. (2004). Dynamic nucleation of Golgi apparatus assembly from the endoplasmic reticulum in interphase hela cells. Traffic 5: 595-605. PubMed ID: 15260829

Kondylis, V. and Rabouille, C. (2003). A novel role for dp115 in the organization of tER sites in Drosophila: J. Cell Biol. 162: 185-198. PubMed ID: 12876273

Kondylis, V., Spoorendonk, K. M. and Rabouille, C., et al. (2005). dGRASP localization and function in the early exocytic pathway in Drosophila S2 cells. Mol. Biol. Cell 16: 4061-4072. PubMed ID: 15975913

Lane, J. D., Lucocq, J., Pryde, J., Barr, F. A., Woodman, P. G., Allan, V. J. and Lowe, M. (2002). Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. J. Cell Biol. 156: 495-509. PubMed ID: 11815631

Marra, P., Maffucci, T., Daniele, T., Tullio, G. D., Ikehara, Y., Chan, E. K., Luini, A., Beznoussenko, G., Mironov, A. and de Matteis, M. A. (2001). The GM130 and GRASP65 Golgi proteins cycle through and define a subdomain of the intermediate compartment. Nat. Cell Biol. 3: 1101-1113. PubMed ID: 11781572

Mogelsvang, S., Gomez-Ospina, N., Soderholm, J., Glick, B. S. and Staehelin, L. A. (2003). Tomographic evidence for continuous turnover of Golgi cisternae in Pichia pastoris. Mol. Biol. Cell 14: 2277-2291. PubMed ID: 12808029

Pelletier, L., Jokitalo, E. and Warren, G. (2000). The effect of Golgi depletion on exocytic transport. Nat. Cell Biol. 2: 840-846. PubMed ID: 11056540

Pelletier, L. et al. (2002). Golgi biogenesis in Toxoplasma gondii. Nature 418: 548-552. PubMed ID: 12152082

Preisinger, C., et al. (2005). Plk1 docking to GRASP65 Plk1 docking to GRASP65 phosphorylated by Cdk1 suggests a mechanism for Golgi checkpoint signalling. EMBO J. 24: 753-765. PubMed ID: 15678101

Puri, S. and Linstedt, A. D. (2003). Capacity of the golgi apparatus for biogenesis from the endoplasmic reticulum. Mol. Biol. Cell 14: 5011-5018. PubMed ID: 14565973

Rossanese, O. W., Soderholm, J., Bevis, B. J., Sears, I. B., O'Connor, J., Williamson, E. K. and Glick, B. S. (1999). Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae. J. Cell Biol. 145: 69-81. PubMed ID: 10189369

Schotman, H,, Karhinen, L. and Rabouille, C. (2008). dGRASP-mediated noncanonical integrin secretion is required for Drosophila epithelial remodeling. Dev. Cell 14: 171-182. PubMed ID: 18267086

Short, B., Preisinger, C., Korner, R., Kopajtich, R., Byron, O. and Barr, F. A. (2001). A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic. J. Cell Biol. 155: 877-883. PubMed ID: 11739401

Shorter, J., Watson, R., Giannakou, M. E., Clarke, M., Warren, G. and Barr, F. A. (1999). GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. EMBO J. 18: 4949-4960. PubMed ID: 10487747

Shorter, J. and Warren, G. (2002). Golgi architecture and inheritance. Annu. Rev. Cell Dev. Biol. 18: 379-420. PubMed ID: 12142281

Slusarewicz, P., Nilsson, T., Hui, N., Watson, R. and Warren, G. (1994). Isolation of a matrix that binds medial Golgi enzymes. J. Cell Biol. 124: 405-413. PubMed ID: 8106542

Sutterlin, C., Hsu, P., Mallabiabarrena, A. and Malhotra, V. (2002). Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells. Cell 109: 359-369. PubMed ID: 12015985

Wang, Y., Seemann, J., Pypaert, M., Shorter, J. and Warren, G. (2003). A direct role for GRASP65 as a mitotically regulated Golgi stacking factor. EMBO J 22: 3279-3290. PubMed ID: 12839990

Wang, Y., Satoh, A. and Warren, G. (2005). Mapping the functional domains of the golgi stacking factor GRASP65. J. Biol. Chem. 280: 4921-4928. PubMed ID: 15576368

Ward, T. H., Polishchuk, R. S., Caplan, S., Hirschberg, K. and Lippincott-Schwartz, J. (2001). Maintenance of Golgi structure and function depends on the integrity of ER export. J. Cell Biol. 155: 557-570. PubMed ID: 11706049

Yoshimura, S. I., Nakamura, N., Barr, F. A., Misumi, Y., Ikehara, Y., Ohno, H., Sakaguchi, M. and Mihara, K. (2001). Direct targeting of cis-Golgi matrix proteins to the Golgi apparatus. J. Cell Sci. 114: 4105-4115. PubMed ID: 11739642

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Biological Overview

date revised: 31 December 2008

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