Through the EVH1 domain, mammalian Homer-related proteins interact in vivo with at least three different group of proteins, Shank/ProSAP, Group I mGluRs, and the InsP3R (Brakeman, 1997; Tu, 1998; Naisbitt, 1999; Tu, 1999). To determine whether such interactions might exist in Drosophila, a yeast two-hybrid bait was constructed consisting of the Homer EVH1 domain fused to the DNA-binding domain of the GAL4 transcription factor. A mutated Homer EVH1 bait (mutEVH) was constructed by introducing several amino acid substitutions in the EVH1 domain. Noteworthy is the substitution of the second glycine in the conserved GLGF motif for a histidine. The crystal structure of the vertebrate Homer-1 EVH1 domain bound to its binding-peptide has shown that any residue other than glycine at this position (position 89 of Homer-1) would be likely to sterically interfere with binding of Homer to its partners (Diagana, 2000).
From a yeast two-hybrid screen of a Drosophila embryonic library using the Homer EVH1 domain as bait, the single fly ortholog of the vertebrate Shank proteins was isolated. Like the vertebrate Shank proteins, Drosophila Shank contains the Homer-binding consensus motif PPxxF near its C terminus. The Homer EVH1 domain shows interaction with the C terminus of Drosophila Shank in the yeast two-hybrid assay. In contrast to the wild-type Homer EVH1 domain, mutEVH fails to interact with Shank C terminus, consistent with the introduced EVH1 mutations abolishing binding. As expected, neither the Homer EVH1 domain nor mutEVH showed any interaction with the C terminus of the characterized Drosophila Group II DmGluRA (Parmentier, 1996), which like vertebrate Group II mGluRs lacks any Homer binding site consensus sequence. These results argue that the ability of Homer to bind Shank is dependent on an intact EVH1 domain and further suggest that at least one of the protein-protein interactions mediated by the EVH1 domain of Homer-related proteins has been evolutionarily conserved (Diagana, 2000).
Homer colocalizes with the synaptic marker Synaptotagmin (see Drosophila Syntaxin) in the dorsal-most region of the neuropil. The regional colocalization of Homer and Synaptotagmin dorsally in the VNC neuropil suggests that Homer is concentrated in synapse-rich regions. Because little or no Homer was detected in the axons of motor neurons and sensory neurons, it seemed possible that Homer might be localized to dendrites. To investigate this possibility an epitope-tagged version of Homer (Homer-myc) was created by fusing six c-myc epitopes to the C-terminal end of the protein. Homer-myc-green fluorescent protein (GFP) was also created, in which six myc epitopes plus the GFP were similarly fused to the C terminus. The two epitope-tagged versions of Homer gave identical results in all the described experiments. The GAL4/UAS transactivation system was used. Homer-myc and Homer-myc-GFP were cloned downstream of the UAS regulatory sequences in the pUASt transformation vector, and multiple transformant lines were generated for each. To express Homer-myc in single neurons, the RCC-GAL4 line, which stochastically expresses GAL4 in a small subset of identified neurons, including aCC, pCC, and RP2, was used. When expressed in the aCC neuron using the RCC GAL4 driver, Homer-myc staining is detected primarily in the ipsilateral and contralateral dendritic arborizations, with little or no staining seen in the axon. This result indicates that Homer is primarily targeted to dendritic processes and thus might function postsynaptically (Diagana, 2002).
To determine the importance of the EVH1 domain for Homer subcellular localization, mutEVH-Homer-myc was created by introducing in the EVH1 domain the same amino acid substitutions that disrupt binding of the Homer EVH1 domain to Shank. When expressed in the aCC neuron using the RCC-GAL4 driver, mutEVH-Homer-myc fails to label the dendrites and instead remains in the cell body. When expressed in the PNS using the pan-neuronal C155 GAL4 driver, Homer-myc has a punctate distribution in many neuronal cell bodies, similar to the pattern characteristic of endogenous Homer. Double-immunofluorescence staining has confirmed that in these cells, Homer-myc colocalizes with the ER compartment marker BiP. In contrast to Homer-myc, mutEVH-Homer-myc fails to show the characteristic punctate ER distribution in PNS neurons and instead is evenly distributed throughout the cytoplasm. Taken together, these results demonstrate that the EVH1 domain of Homer is required for its subcellular localization and further suggests that this localization may be mediated by one of the binding partners of Homer (Diagana, 2002).
Transport, translation, and anchoring of osk mRNA and proteins are essential for posterior patterning of Drosophila embryos. Homer and Bifocal act redundantly to promote posterior anchoring of the osk gene products. Disruption of actin microfilaments, which causes delocalization of Bifocal but not Homer from the oocyte cortex, severely disrupts anchoring of osk gene products only when Homer (not Bifocal) is absent. The data suggest that two processes, one requiring Bifocal and an intact F-actin cytoskeleton and a second requiring Homer but independent of intact F-actin, may act redundantly to mediate posterior anchoring of the osk gene products (Babu, 2004).
Both Bif and Hom show asymmetric localization at the apical cortex of embryonic neuroblasts, indicating that these F-actin binding proteins may be involved in neuroblast asymmetric divisions. However, animals lacking both the maternal and zygotic components of either gene are fertile, viable, and show no obvious defects in embryonic CNS development. This prompted construction of double mutants of bif and hom. However, although double homozygous mutant females are viable, they show defects in oogenesis, with the vast majority of the eggs produced remaining unfertilized, as judged by the lack of staining in eggs using an antibody directed against the sperm tail. In the few fertilized embryos that do undergo development, the numbers of Vasa positive germ cells are drastically reduced, suggesting possible defects in the function or localization of posterior determinants during oogenesis (Babu, 2004).
Analyses of bif and hom single mutants as well as double mutant oocytes indicate that the two genes act in a redundant manner for the correct anchoring of posteriorly but not anteriorly localized molecules. In stage 10 oocytes, posterior group molecules, including oskar (osk) RNA, the two isoforms of Osk proteins, Staufen (Stau), and a fusion protein in which ß-galactosidase has been fused to the N-terminal extension of the long form of the Osk protein (referred to as Osk-ßGal, used as a marker for the long form of the Osk protein, which has been shown to have a role in the posterior cortical maintenance of Osk), are all localized as tight posterior cortical crescents in wild-type oocytes. In most double mutant oocytes, these molecules, when detectable, are present largely at the posterior region; however in contrast to wild-type oocytes, they show a diffuse distribution that extends into regions of the posterior cytoplasm distinctly interior to the posterior cortex. In about 30% of the cases, Osk or Stau protein cannot be detected. The defects seen in the oocytes of double mutants are essentially absent in the single mutant oocytes. These findings indicate that whereas bif and hom are individually dispensable, together they are required for the localization of the posterior components of the oocytes. These defects in localization are specific for the posterior group molecules, because the anterior/dorsal localization of Gurken and anterior localization of bicoid RNA are unaffected (Babu, 2004).
Not surprisingly, staining with anti-Bif and anti-Hom antibodies indicates that both proteins are expressed in the oocyte. Bif localizes to the oocyte cortex in a manner very similar to that seen for F-actin. The staining seen with the anti-Hom antibody is highly punctated and, although localization is cortically enriched, Hom is also present in the cytoplasm. The cortical staining seen in wild-type oocytes (and nurse cells) is absent in mutant oocytes stained with the corresponding antibodies, confirming the specificity of both antibodies and that the mutant alleles do not produce detectable amounts of protein. Since homLL17 is a complete deletion of the coding region and bifR47 removes a significant portion of the coding region, they are both likely to be null alleles (Babu, 2004).
Several observations indicate that the defect in posterior localization of the osk gene products is due to defective anchoring and not transport or translation of osk RNA. Osk RNA and Osk proteins as well as Stau are localized normally in stage 9 double mutant oocytes. Consistent with this, both the F-actin and microtubule cytoskeletons in the double mutants are indistinguishable from those in the wild-type oocytes. Not only does the polarity of the microtubules appear normal, as assayed using a kinesin heavy chain (khc) ß-Gal marker, the cytoskeleton-dependent cytoplasmic streaming is also absent in stage 9 oocytes and occurs normally in stage 10 double mutant oocytes, as is seen with wild-type oocytes. Taken together, these observations indicate that the double mutant oocytes retain, at a gross level, normal cytoskeletal structure. They can transport osk mRNA to the posterior cortex, and translate it appropriately, but do not maintain the posterior anchoring of the osk gene products (Babu, 2004).
An intact F-actin cytoskeleton is thought to be required for asymmetric protein localization in several contexts. In the oocyte, loss or reduction of the actin binding proteins moesin and tropomyosin have been shown to affect the posterior anchoring of Osk in the oocyte and the embryo, respectively. To assess the requirement for an intact microfilament cytoskeleton for the anchoring of osk RNA and proteins in the oocyte, the localization of these molecules was examined in wild-type oocytes treated with an actin depolymerizing drug, Latrunculin A (Lat A). Following treatment with 20 µm Lat A, cortical F-actin in the oocytes was largely undetectable with phalloidin, yet, unexpectedly, both Osk proteins (short and Osk-ßGal) and osk RNA remain localized to the posterior cortex of the great majority of wild-type oocytes from stage 9-10B. This was seen even when the oocytes were overstained for the osk RNA: in around 17% of the Lat A-treated wild-type oocytes, mild defects in anchoring are observed. osk RNA and proteins show a diffuse localization at the posterior cortex. However, in no cases were they seen concentrated in the cytoplasm or had they become delocalized or undetectable (as seen in the hom/bif double mutant oocytes) as would be expected if an intact F-actin cytoskeleton were to be an absolute requirement for the normal anchoring of Osk. These mild effects on protein localization in the oocyte are in distinct contrast to those seen in embryonic neuroblasts where severe and high-penetrance defects in asymmetric protein localization are observed following disruption of microfilaments. These observations suggest that the role of microfilaments in the anchoring of proteins to the cortex may differ in the different cellular contexts (Babu, 2004).
Additional experiments were performed to ascertain whether the mild effects on Osk posterior anchoring following disruption of microfilaments are peculiar to Lat A treatment. In fact, the posterior cortical localization of Osk remained in the great majority of oocytes even after treatment with cytochalasin D (CD), Lat A followed by CD, CD followed by Lat A, and up to 100 µM Lat A. These results are consistent with previous reports of CD disruption of F-actin, for example. However, they indicate that an intact F-actin cytoskeleton, although required for the normal posterior anchoring of Osk in a small proportion of oocytes, is probably not the only factor involved in normal anchoring of Osk to the posterior cortex. There are at least two possible explanations for these observations. First, a small amount of residual F-actin might remain even after sequential treatment with Lat A and CD, which is sufficient to anchor Osk normally in a small fraction of the drug-treated oocytes. Alternatively, there may be other factors besides an intact F-actin cytoskeleton, which can, in parallel, contribute toward the posterior anchoring of osk RNA and proteins (Babu, 2004).
The requirement for intact microfilaments on Hom and Bif localization was assessed. Both Bif and Hom localize to the cortex (and in the case of Hom also the cytoplasm) of wild-type oocytes. Following depolymerization of F-actin with Lat A, such that cortical F-actin becomes undetectable in the oocyte, Hom localization appears unchanged from the wild-type pattern in all oocytes, but Bif becomes highly diffuse with essentially no detectable enrichment at the cortex. This appears to be an effect on Bif localization and not stability, because the levels of the protein are not reduced as judged by Western blot analysis. Treating oocytes with colchicine, which disrupts the microtubules, did not affect either Hom or Bif localization in the oocyte. These findings raise the possibility that bif function might be dependent on intact F-actin; however, Hom localization is Lat A-insensitive, suggesting that its function in the oocyte may not require intact microfilaments. However, the possibility cannot be excluded that Lat A treatment allows for the retention of a small amount of the F-actin cytoskeleton, and this is stabilized in some way by Hom (Babu, 2004).
These data raise the possibility that there might be two processes, one that is microfilament-dependent and requires Bif, and another which is not dependent on intact microfilaments and requires Hom. Either process is sufficient to anchor the osk gene products to the posterior cortex of the great majority of the oocytes. One prediction of this hypothesis is that hom should be necessary to anchor posterior components in the absence of intact F-actin. Indeed, when hom single mutant oocytes were treated with Lat A, a large amount of cytoplasmic Osk was found at stage 9 and 10 near the posterior pole, and there was a large reduction in the Osk-ßGal signal. This could indicate that the loss of the longer Osk isoform may be the primary defect seen in Lat A-treated hom mutants; this longer Osk isoform is known to be essential for osk RNA and protein anchoring. The defects induced by depolymerizing F-actin in hom oocytes are similar to but more severe than those seen in bif;hom double mutant oocytes. This is probably due to the fact that F-actin disruption also leads to premature streaming in stage 9 and enhanced streaming in stage 10 oocytes, thus accentuating the effects of the loss of Osk anchoring at the posterior cortex (Babu, 2004).
The above results demonstrate that disruption of F-actin in the absence of hom function disrupts anchoring of the osk gene products. Similar results were obtained when hom mutants were treated with just CD or treated successively with Lat A and CD or vice versa. CD does not cause loss of F-actin as seen with phalloidin staining, and causes changes in the cortical F-actin as well as causing some of the F-actin to be seen in the cytoplasm. This latter effect is not seen with Lat A. This could be attributed to the difference in the mechanism of action between CD and Lat A. However, despite this difference between CD and Lat A, the effects of these drugs singly or in combination on Osk posterior anchoring are similar, causing mild defects in Osk posterior anchoring in only one-fifth of the treated wild-type oocytes and severe defects in the great majority of treated hom oocytes (Babu, 2004).
A second prediction is that disruption of microfilaments in the absence of bif should not affect anchoring of Osk. Indeed, most wild-type and bif single mutant oocytes treated with Lat A show largely wild-type anchoring of the Osk gene products, similar to Lat A treatment of wild-type oocytes. These results are consistent with the notion that Bif functions in an F-actin-dependent manner in maintaining Osk to the posterior of the oocyte (Babu, 2004).
If there are two independent mechanisms that act redundantly for normal Osk anchoring at the posterior cortex, then it would follow that the bif;hom double mutants in the absence of an intact F-actin cytoskeleton would show a phenotype similar to that of hom single mutants treated with Lat A, and not a more severe phenotype. This is indeed the case that is observed on testing osk RNA and Osk proteins in Lat A-treated double mutant oocytes (Babu, 2004).
In light of the finding that Hom posterior cortical localization remains unchanged following F-actin disruption, its ability to localize Osk to the posterior may be because it forms a complex with Osk. Co-immunoprecipitation experiments, using Drosophila ovarian extracts, indicate that Hom and Osk form a complex in vivo. Further, the stability of this complex is not dependent on an intact F-actin cytoskeleton (Babu, 2004).
The maintenance of Osk at the posterior of the oocyte may be mediated by two distinct mechanisms, either of which is sufficient, at least for the great majority of the oocytes. One mechanism does not require an intact F-actin cytoskeleton, and Hom seems to be an important player in this process. Hom can complex with Osk, and the stability of this complex is not dependent on an intact F-actin cytoskeleton. The second mechanism requires an intact F-actin cytoskeleton. Bif seems to be required for this mechanism. Overexpression of Bif can promote actin polymerization in cultured cells. Since it is also known that F-actin forms a complex with Bif in Drosophila embryonic lysates and that Bif binds directly to F-actin filaments in vitro, it is possible that Bif acts to stabilize actin filaments. In this scenario its absence may cause subtle changes in the F-actin cytoskeleton that may affect its capacity to anchor molecules at the cortex when hom is absent. In contrast, hom can function and is required to anchor Osk in the absence of an intact F-actin cytoskeleton or in the absence of bif function. Only when both mechanisms are disrupted in the oocyte, either through the simultaneous disruption of both hom and bif, or when F-actin is disrupted in the absence of hom, do the osk gene products fail to remain anchored to the posterior cortex (Babu, 2004).
Recent studies showed that Drosophila moesin is essential to link the cortical F-actin to the oocyte cell membrane. When moesin function is compromised, cortical F-actin can detach from the cell membrane and "fall" into the oocyte cytoplasm, and this results in the mislocalization of Osk. The effects of loss of moesin function on the localization of both Bif and Hom were examined; in these mutant oocytes, where the cortical F-actin detaches from the mutant oocyte cell membrane, components of both of the proposed anchoring pathways, Hom and Bif, also detach. These observations are consistent both with the Osk mislocalization phenotype seen in moesin mutant oocytes and with the model. It will be interesting to identify additional molecules involved in these separate pathways and to elucidate the mechanisms that are required to localize Hom to the posterior cortex of the oocyte in the absence of an intact actin cytoskeleton (Babu, 2004).
See the embryonic expression pattern of homer at the Berkeley Drosophila Genome Project Patterns of Gene Expression Site.
Whole-mount in situ hybridization was performed using of a full-length DIG-labeled homer antisense probe. A widespread, low-level expression of homer was detected during early embryogenesis. Beginning at stage 12 the levels of homer mRNA increase in the developing CNS and PNS, such that by late stage 16, homer RNA is enriched in the nervous system. Close examination of in situ hybridization performed on dissected embryos shows that within the CNS and PNS of stage 16 embryos, most if not all neurons express homer mRNA (Diagana, 2002).
A polyclonal antibody was raised against Homer that recognizes a 47 kDa protein on a Western blot of protein extracts from adult fly heads. This size is in agreement with the protein predicted from the sequence of homer cDNAs. Two results confirm the specificity of the anti-Homer antibody: (1) no signal can be detected in protein extracts of flies homozygous for a homer loss-of-function allele; (2) the antibody specifically recognizes a truncated version of Homer lacking the C terminus (HomerDeltaC) in protein extracts of flies that express HomerDeltaC in the CNS from a transgene (Diagana, 2002).
Using the anti-Homer antibody, immunofluorescence staining of Drosophila embryos was performed. In wild-type embryos, high levels of Homer expression are detected in the CNS and PNS, with a low level of expression detectable in other tissues, including the epidermis, the gut, and the somatic muscles. As expected, all staining was found to be abolished in embryos homozygous for the homerR102 mutation. Homer expression in the nervous system is maintained throughout development into adulthood, where in the brain it is expressed at high levels within the lamina and the medulla neuropil of the optic lobes and at lower levels in the central brain neuropil (Diagana, 2002).
Within the embryonic ventral nerve cord (VNC), the majority of staining is concentrated in the neuropil regions of each neuromere. Confocal analysis of immunostainings (using anti-Homer and antibodies to HRP) that recognize a neuronal surface epitope present on all axons and dendrites, reveals that Homer is highly enriched in the dorsal-most region of the neuropil. To examine whether this enrichment might represent localization of Homer to synaptic regions, triple labeling for anti-HRP, Homer, and the synaptic protein Synaptotagmin was performed. Synaptotagmin is similarly localized to the dorsal region of the neuropil and Homer extensively colocalizes with it. These results suggest that in Drosophila, Homer is targeted to synapses, similar to the localization of vertebrate Homer proteins (Diagana, 2002 and references therein).
A striking feature of Homer expression is the punctate pattern seen in neuronal cell bodies, a pattern reminiscent of the staining of Golgi stacks. By performing double immunostaining with anti-Homer and antibodies that label the Golgi, Homer labeling was found to partially overlap with the Golgi staining but does not fully colocalize with it. This suggested that Homer is localized in the closely juxtaposed ER. To label the ER compartment, a monoclonal antibody was generated against the rat ER-resident protein that recognizes a Drosophila protein retained in the ER. In double immunostainings anti-Homer staining was found to overlap extensively with the ER marker anti-BiP, arguing for Homer localization in the ER compartment (Diagana, 2002).
In the Berkeley Drosophila Genome Project database, an EP line [EP(2)2141] was identified in which a P element is inserted 60 bp upstream of the first exon of homer. Western blot analysis reveals that homer expression is not significantly reduced in flies homozygous for the EP(2)2141 insertion. To create a mutation in the homer gene, a deletion was generated by excising the P element. A 1.5 kb deletion, homerR102, was recovered that removes the first two exons and half of the third exon of the homer gene. Sequencing across the breakpoints of this deletion revealed that it removes the nucleotides coding for the first 168 amino acids of the Homer protein. The lack of staining on Western blots of protein extract from homerR102 mutants and immunofluorescence staining performed on homerR102 embryos confirmed the nature of the homerR102 allele. For use as a wild-type control, a precise excision of the EP(2)2141 insertion was recovered. The integrity of the homer locus was confirmed in these flies by DNA sequencing across the P-element insertion site. This line is referred to as homer+. The homerR102 and homer+ chromosomes were each placed in identical genetic backgrounds for all studies of homer mutation (Diagana, 2002).
homerR102 homozygous flies are viable and fertile. In addition, they do not display any obvious uncoordinated phenotype and are able to respond to visual stimuli that elicit the escape response. Thus, Homer does not appear to be required for general aspects of nervous system development, nor does it appear to play a critical role in basic synaptic transmission. Adult flies display no gross anatomical defects, and the overall organization of the nervous system is indistinguishable from wild type, as assessed with anti-HRP antibodies. Moreover, no defects in axon pathfinding during the development of the embryonic nervous system of homerR102 mutants were detected as assayed with anti-Fasciclin II (mAb 1D4) and mAb 22C10, both of which recognize discrete subsets of axons, and no defects were detected with mAb BP102, which labels all CNS axons (Diagana, 2002).
It has been reported that overexpression of Homer in the Xenopus developing nervous system results in aberrant axon pathfinding (Foa, 2001). Thus, it was asked whether overexpression of Drosophila Homer throughout the developing CNS would result in abnormal axonal pathfinding. Immunostaining of the ventral nerve cord of embryos carrying one copy of the pan-neuronal C155-GAL4 driver and one copy of the UAS:homer-myc transgene was performed. No pathfinding errors were detected as assayed with anti-Fasciclin II, mAb 22C10, mAb BP102, and anti-HRP. Together, these loss- and gain-of-function data strongly suggest that Homer does not play a major axon guidance role in the Drosophila embryonic nervous system (Diagana, 2002).
Ageta, H., et al. (2001). Regulation of the level of Vesl-1S/Homer-1a proteins by ubiquitin-proteasome proteolytic systems. J. Biol. Chem. 276(19): 15893-7. 11278836
Ango, F., et al. (2000). Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by Homer1 proteins and neuronal excitation. J Neurosci 20: 8710-8716. 11102477
Ango, F., et al. (2002).Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons. Mol. Cell. Neurosci. 20(2): 323-9. 12093163
Babu, K., Cai, Y., Bahri, S. Yang, X. and Chia, W. (2004). Roles of Bifocal, Homer, and F-actin in anchoring Oskar to the posterior cortex of Drosophila oocytes. Genes Dev. 18: 138-143. 14752008
Beneken, J., et al. (2000). Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Neuron 26(1): 143-54. 10798399
Bottai, D., et al. (2000). Synaptic activity-induced conversion of intronic to exonic sequence in Homer 1 immediate early gene expression. J. Neurosci. 22(1): 167-75. 11756499
Brakeman, P. R., et al. (1997). Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386: 284-288. 9069287
Diagana, T. T., (2002). Mutation of Drosophila homer disrupts control of locomotor activity and behavioral plasticity J. Neurosci. 22(2): 428-436. 11784787
Feng, W., et al. (2002). Homer regulates gain of ryanodine receptor type 1 channel complex. J. Biol. Chem. 12223488
Foa, L., et al. (2001). The scaffold protein, Homer 1b/c, regulates axon pathfinding in the central nervous system in vivo. Nat. Neurosci. 4: 499-506. 11319558
Irie, K., et al. (2002). Crystal structure of the Homer 1 family conserved region reveals the interaction between the EVH1 domain and own proline-rich motif. J. Mol. Biol. 318(4): 1117-26. 12054806
Kammermeier, P. J., et al. (2000). Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels. J. Neurosci. 20(19): 7238-45. 11007880
Kato, A., et al. (1998). Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. J. Biol. Chem. 273: 23969-223975. 9727012
Naisbitt, S., et al. (1999). Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23: 569-582. 10433268
Parmentier, M. L., Pin, J. P., Bockaert, J. and Grau, Y. (1996). Cloning and functional expression of a Drosophila metabotropic glutamate receptor expressed in the embryonic CNS. J. Neurosci. 16: 6687-6694. 8824309
Roche, K. W., et al. (1999). Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. J Biol Chem 274: 25953-25957. 10464340
Sala, C., et al. (2001). Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31: 115-130. 11498055
Shin, D. M., et al. (2003). Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities. J. Cell Biol. 162(2): 293-303. 12860966
Shiraishi, Y., et al. (1999). Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. J. Neurosci. 19: 8389-8400. 10493740
Suzuki, T., et al. (2004). A novel scaffold protein, TANC, possibly a rat homolog of Drosophila Rolling pebbles (Rols), forms a multiprotein complex with various postsynaptic density proteins. Eur. J. Neurosci. 21(2): 339-50. 15673434
Szumlinski, K. K., et al. (2004). Homer proteins regulate sensitivity to cocaine. Neuron 43(3): 401-13. 15294147
Tadokoro, S., et al. (1999). Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl- 1L) in group 1 metabotropic glutamate receptor clustering. Proc. Natl. Acad. Sci. 96: 13801-13806. 10570153
Thomas, U. (2002). Modulation of synaptic signalling complexes by Homer proteins. J. Neurochem. 81(3):407-13. 12065649
Tu, J. C., et al. (1998). Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21: 717-726. 9808459
Tu, J. C., et al. (1999). Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23: 583-592. 10433269
Xiao, B., et al. (1998). Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins. Neuron 21: 707-716. 9808458
Xiao, B., Tu, J. C. and Worley, P. F. (2000). Homer: a link between neural activity, glutamate receptor function. Curr. Opin. Neurobiol. 10: 370-374. 10851183
date revised: 5 March 2005
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