short stop/kakapo


Plectin: homologous to the N-terminal domain of Kakapo

Plakins are cytoskeletal linker proteins initially thought to interact exclusively with intermediate filaments (IFs), but which have recently been found to associate additionally with actin and microtubule networks. Plakins are enormous (200-700 kD) coiled-coil dimeric proteins that include desmoplakin, bullous pemphigoid antigen (BPAG), plectin, periplakin, and envoplakin, and which are typified by their ability to associate with intermediate filaments (IFs) through their carboxy tail segments. Through defined interacting domains, plakins make cross-bridges between IFs and adhesive junctions that specifically associate with this cytoskeletal component. Thus, for example, plectin and BPAG1e (the epithelial form of BPAG1) each bind to proteins in hemidesmosomes as well as IFs, whereas desmoplakin associates with components of desmosomes in addition to IFs. Periplakin and envoplakin differ in that they are expressed only in terminally differentiating epidermal cells, where they appear to cross-link desmosomes and IFs to the cornified envelope. Plakin functions have been examined through gene knockout technology, and in some organs, particularly skin, these connector molecules seem to play structural roles that partially overlap with those of the IFs to which they connect. Thus, the loss of either BPAG1 or plectin severs keratin IFs from hemidesmosomes and the epithelium can no longer withstand mechanical shear forces, resulting in intraepidermal rupturing and a skin blister. In humans, this condition is known as epidermolysis bullosa simplex, most frequently caused by IF-disrupting mutations in the keratins themselves. Reflective of additional expression of the BPAG1 gene in sensory neurons, mice defective in the BPAG1 gene exhibit axonal swellings packed with disorganized IFs and accompanied by gross neuronal degeneration. Similarly, humans defective in the plectin gene display signs of muscular dystrophy, reflective of plectin’s additional expression in muscle. These findings underscore the importance of plakins in cell integrity and in maintaining IF cytoarchitecture (Karakesisoglou, 2000 and references therein).

Most plakin genes encode multiple isoforms that are differentially expressed in a tissue-specific manner. An interesting feature of plakins is that the isoforms perform functions uniquely tailored to suit the cytoskeletal needs of each specialized cell. Some isoforms are not limited to interconnections with IFs, but can also associate with the other cytoskeletal networks. Two neuronal forms of BPAG1 have the capacity to bind simultaneously to actin and neuronal IF networks, perhaps anchoring the neuronal IF cytoskeleton to the cortical actin microfilaments lining the axon. Plectin also associates with actin and IF networks, but in this case, it may function in actin dynamics, as cultured plectin null fibroblasts display perturbations in cell motility and Rho/Rac/Cdc42-mediated actin rearrangements. Some plakins have the capacity to bridge IFs and MTs, as was first visualized by immunoelectron microscopy of cultured fibroblasts, whose actin cytoskeleton had been disrupted and extracted. An MT binding site has now been identified in BPAG1n3, a novel neural isoform that appears to function by stabilizing the network to facilitate axonal transport over long distances. An extraordinary feature of this plakin is that when NFs are removed from sensory neurons through gene targeting, BPAG1n3 still associates with MTs, classifying this protein as a bona fide MT-associated protein, or MAP (Karakesisoglou, 2000 and references therein).

ACF7 is a mammalian ortholog of the Drosophila Kakapo plakin. While ACF7/kakapo is divergent from other plakins in its IF-binding domain, it has at least one actin (Kd 5 0.35 mM) and one microtubule (Kd z6 mM) binding domain. ACF7/kakapo isoforms contain two features distinguishing them from the other plakins: (1) the 3,000 to 4,000 amino acid central domain, which has similarities to the spectrinlike repeats of dystrophin and to the coiled-coil rod segment of plakins necessary for oligomerization, and (2) the 500 residue tail, which harbors sequence homology to the EF-hand calcium binding domain of dystrophin as well as to Gas2, a protein selectively expressed in growth-arrested cells and associated with the actin filament network. In addition, the majority of the head segment, including the 215 residue putative actin binding domain (ABD) of isoforms 1 and 2 and the 1,184 residue midsegments (M1 and M2) of all three ACF7 isoforms, are similar in sequence to plectin and BPAG1 neural isoforms. Isoform 3 of ACF7 is similar to BPAG1n3 in that it is distinguished by the absence of the amino-terminal half of the ABD (Karakesisoglou, 2000).

Similar to its fly counterpart, ACF7 is expressed in the epidermis. In well spread epidermal keratinocytes, ACF7 discontinuously decorates the cytoskeleton at the cell periphery, including microtubules (MTs) and actin filaments (AFs) that are aligned in parallel converging at focal contacts. Upon calcium induction of intercellular adhesion, ACF7 and the cytoskeleton reorganize at cell-cell borders but with different kinetics from adherens junctions and desmosomes. Treatments with cytoskeletal depolymerizing drugs reveal that ACF7’s cytoskeletal association is dependent upon the microtubule network, but ACF7 also appears to stabilize actin at sites where microtubules and microfilaments meet. It is posited that ACF7 may function in microtubule dynamics to facilitate actin-microtubule interactions at the cell periphery and to couple the microtubule network to cellular junctions. These attributes provide a clear explanation for the kakapo mutant phenotype in flies (Karakesisoglou, 2000).

The cloning of Drosophila kakapo has provided the first insights into the existence and function of plakins in lower eukaryotic organisms (Gregory, 1998). Kakapo mutants were identified in a genetic screen for flies defective in PS integrin-mediated cell-substratum adhesion. Kakapo is expressed in fly epidermal cells that attach to underlying muscle through PS integrin junctions called hemiadherens junctions (Gregory, 1998; Prokop, 1998). The closest parallel between hemiadherens junctions in Drosophila and intercellular and cell-substratum junctions of mammalian epidermis has been proposed to be hemidesmosomes, which have at their core the integrin alpah6beta4 and which bind selectively to the keratin IF network. Hemidesmosomes bind two IF-anchoring plakins, plectin and BPAG1e: when these are absent, epidermal rupturing occurs. Fly epidermal cells lack keratin IFs, and appear to utilize MTs instead for the bulk of their mechanical integrity, including those MTs provided by cytoskeletal attachment to PS integrins (Gregory, 1998; Prokop, 1998). This led to the postulate that Kakapo might link actin and MT cytoskeletons to the PS integrin-mediated adhesion junctions (Gregory, 1998). This said, Kakapo is found at both basal and apical surfaces of the epidermal cells, in contrast to PS integrins, which are restricted to the basal surface of fly epidermis. In this regard, it would seem that Kakapo’s functions extend beyond those of anchoring the cytoskeleton to PS integrins (Karakesisoglou, 2000).

A test of was made of some of the hypotheses derived from the kakapo mutant phenotype in flies. Evidence has now been provided that ACF7 is a MT-binding protein; this provides insights into why kakapo mutants cause ultrastructural perturbations in cytoskeletal networks of fly epidermal muscle attachment cells (Prokop, 1998). What is the function(s) of Kakapo in mammalian epidermal cells and where is it involved? While unequivocal assessment of function awaits gene targeting approaches, it was intriguing to find that ACF7 localizes to the plus ends of a subset of MTs that associate with focal adhesion contacts. In epidermal keratinocytes, focal adhesion contacts are composed largely of alpha3beta1 integrins, and interestingly, PS integrins are more similar in sequence to the alpha-beta1 integrins of mammalian cells than they are to aalpha6beta4 integrins. Also relevant is the recent finding that mammalian focal adhesion contacts associate with MTs as well as to the actin cytoskeleton, in contrast to hemidesmosomes, which seem to be restricted to keratin IFs in their cytoskeletal attachments. Taken together, these findings suggest that in mammalian epidermal cells, ACF7 functions in a fashion that is in fact similar to the role hypothesized for Kakapo based upon its mutant phenotype in flies. At mammalian focal adhesions, MTs appear to be connected after integrin clustering and attachment of actin cytoskeleton. This led to the postulate that AFs at mammalian focal adhesions might tether approaching MTs, thereby orienting their growth and stabilizing them. Given that ACF7 has a functional ABD, but seems to predominantly associate with radial ends of MTs, the findings raise the possibility that perhaps these MTs carry their own actin-tethering ability to focal adhesions rather than the reverse. This process could be regulated in a dynamic way, particularly if binding of ACF7 to MTs is necessary to unmask the ACF7 actin binding domain. Future studies will be necessary to assess the extent to which this provocative notion might be correct. These results raise the possibility that ACF7 may function in part by mediating the organization of the MT cytoskeleton through its ability to make connections with the actin cytoskeleton. Connections between MTs and actin have long been postulated, but ACF7 is the first broadly expressed protein with the demonstrated ability to bind to both networks. In addition, ACF7 seems to possess the ability to selectively restrict these interactions, since only a small fraction of the actin and MT networks display ACF7 decoration. While this includes the AFs and MTs associated with focal contacts, the connections of ACF7 to the cytoskeleton clearly extends beyond these interactions. In this regard, the broader localization of ACF7 is reminiscent of the localization of Kakapo to both the basal and apical surfaces of epidermal cells, despite restriction of PS integrins to basal surfaces (Karakesisoglou, 2000).

Plectin and its isoforms are versatile cytoskeletal linker proteins of very large size (>500 kDa) that are abundantly expressed in a wide variety of mammalian tissues and cell types. Earlier studies indicated that plectin molecules are associated with and/or directly bound to subcomponents of all three major cytoskeletal filament networks, the subplasma membrane protein skeleton, and a variety of plasma membrane-cytoskeleton junctional complexes, including those found in epithelia, various types of muscle, and fibroblasts. In conjunction with biochemical data, this led to the concept that plectin plays an important role in cytoskeleton network organization, with consequences for viscoelastic properties of the cytoplasm and the mechanical integrity and resistance of cells and tissues. Several recent findings lend strong support to this concept. A hereditary disease, epidermolysis bullosa simplex (EBS)-MD, characterized by severe skin blistering combined with muscular dystrophy, is caused by defects in the plectin gene. Plectin-deficient mice die shortly after birth, and exhibit severe defects in skin, skeletal muscle and heart. In vitro studies with cells derived from such animals unmask an essential new role of plectin as regulator of cellular processes involving actin stress fibers dynamics. Comprehensive analyses of the gene locus in man, mouse, and rat point towards a complex gene expression machinery, comprising an unprecedented diversity of differentially spliced transcripts with distinct 5' starting exons, probably regulated by different promoters. This could provide a basis for cell type-dependent and/or developmentally-controlled expression of plectin isoforms, exerting different functions through binding to distinct partners. Based on its versatile functions and structural diversification, plectin emerges as a prototype cytolinker protein among a family of proteins sharing partial structural homology and functions (Wiche, 1998).

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. Cloning of a candidate dt gene, dystonin, is described that is predominantly expressed in the dorsal root ganglia and other sites of neurodegeneration in dt mice. Dystonin encodes an N-terminal actin binding domain and a C-terminal portion comprised of the hemidesmosomal protein, bullous pemphigoid antigen 1 (bpag1). dt and bpag1 are part of the same transcription unit which is partially deleted in a transgenic strain of mice, Tg4, that harbours an insertional mutation at the dt locus, and in mice that carry a spontaneous dt mutation, dtAlb. Abnormal dystonin transcripts are demonstrated in a second dt mutant, dt24J. It is concluded that mutations in the dystonin gene are the primary genetic lesion in dt mice (Brown, 1995).

BPAG1 is the major antigenic determinant of autoimmune sera of bullous pemphigoid (BP) patients. It is made by stratified squamous epithelia, where it localizes to the inner surface of specialized integrin-mediated adherens junctions (hemidesmosomes). To explore the function of BPAG1 and its relation to BP, the removal of the BPAG1 gene was targetted in mice. Hemidesmosomes are otherwise normal, but they lack the inner plate and have no cytoskeleton attached. Though not affecting cell growth or substratum adhesion, this compromises mechanical integrity and influences migration. Unexpectedly, the mice also develop severe dystonia and sensory nerve degeneration typical of dystonia musculorum (dt/dt) mice. In at least one other strain of dt/dt mice, BPAG1 gene is defective (Guo, 1995).

The gene responsible for the mouse neurological disorder dystonia musculorum has been cloned. The predicted product of this gene, dystonin (Dst), is a neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin binding domain. Mouse ACF7 shows extended homology with both the actin binding domain (ABD) and the Bpag1 portions of dystonin. Moreover, mACF7 and Dst display similar isoform diversity and encode similar sized transcripts in the nervous system. Phylogenetic analysis of mACF7 and dystonin ABD sequences suggests a recent evolutionary origin and that these proteins form a separate novel subfamily within the beta-spectrin superfamily of actin binding proteins. Given the implication of several actin binding proteins in genetic disorders, it is important to know the pattern of mACF7 expression. mACF7 transcripts are detected principally in lung, brain, spinal cord, skeletal and cardiac muscle, and skin. Intriguingly, mACF7 expression in lung is strongly induced just before birth and is restricted to type II alveolar cells. To determine whether spontaneous mutants that may be defective in mACF7 exist, the mACF7 gene was mapped to mouse chromosome 4 (Bernier, 1996).

Plectin is a widely expressed high molecular weight protein that is involved in cytoskeleton-membrane attachment in epithelial cells, muscle, and other tissues. The human autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (MD-EBS) shows epidermal blister formation at the level of the hemidesmosome and is associated with a myopathy of unknown etiology. Plectin is absent in skin and cultured keratinocytes from an MD-EBS patient, suggesting that plectin is a candidate gene/protein system for MD-EBS mutation. The 14800-bp human plectin cDNA was cloned and sequenced. The predicted 518-kD polypeptide has homology to the actin-binding domain of the dystrophin family at the amino terminus, a central rod domain, and homology to the intermediate filament-associated protein desmoplakin at the carboxyl terminus. The corresponding human gene (PLEC1), consisting of 33 exons spanning >26 kb of genomic DNA was cloned, sequenced, and mapped to chromosomal band 8q24. Homozygosity by descent is observed in the consanguineous MD-EBS family with intragenic plectin polymorphisms. Direct sequencing of PCR-amplified plectin cDNA from the patient's keratinocytes revealed a homozygous 8-bp deletion in exon 32 causing a frameshift and a premature termination codon 42 bp downstream. The clinically unaffected parents of the proband are heterozygous carriers of the mutation. These results establish the molecular basis of MD-EBS in this family and clearly demonstrate the important structural role for plectin in cytoskeleton-membrane adherence in both skin and muscle (McLean, 1996).

The cornified envelope is a layer of transglutaminase cross-linked protein that is assembled under the plasma membrane of keratinocytes in the outermost layers of the epidermis. The cDNA sequence was determined of one of the proteins, which becomes incorporated into the cornified envelope of cultured epidermal keratinocytes. The protein has an apparent molecular mass of 195 kD and is encoded by a mRNA with an estimated size of 6.3 kb. The protein is expressed in keratinizing and nonkeratinizing stratified squamous epithelia and in a number of other epithelia. Expression of the protein is upregulated during the terminal differentiation of epidermal keratinocytes in vivo and in culture. Immunogold electron microscopy was used to demonstrate an association of the 195-kD protein with the desmosomal plaque and with keratin filaments in the differentiated layers of the epidermis. Sequence analysis shows that the 195-kD protein is a member of the plakin family of proteins, to which envoplakin, desmoplakin, bullous pemphigoid antigen 1, and plectin belong. Envoplakin and the 195-kD protein coimmunoprecipitate. Analysis of their rod domain sequences suggests that the formation of both homodimers and heterodimers would be energetically favorable. Confocal immunofluorescent microscopy of cultured epidermal keratinocytes revealed that envoplakin and the 195-kD protein form a network radiating from desmosomes, and it is speculated that the two proteins may provide a scaffolding onto which the cornified envelope is assembled. The 195-kD protein has been named periplakin (Ruhrberg, 1997b).

The bullous pemphigoid antigen BPAG1 is required for keratin filament linkage to the hemidesmosome, an adhesion complex in epithelial basal cells. BPAG1 structural organization is similar to the intermediate filament-associated proteins desmoplakin I (DPI) and plectin. All three proteins have predicted dumbbell-like structure with central alpha-helical coiled-coil rod and regions of N- and C-terminal homology. To characterize the size of the N-terminal globular domain in BPAG1, two polypeptides spanning possible boundaries with the coiled-coil rod domain of BPAG1 were expressed in Escherichia coli. BP-1 (Mr = 111,000), containing amino acids 663-1581 of BPAG1, and BP-1A, with a 186 amino acid N-terminal deletion, were purified. BP-1 and BP-1A behave as highly asymmetric dimers in aqueous solution according to velocity sedimentation and gel filtration. Both have globular heads with rod-like tails of roughly equal length, 55-60 nm, upon rotary shadowing. BP-1A content of alpha-helix, determined by circular dichroism, is approximately 90%, consistent with alpha-helical coiled-coil formation in the rod-like tails. The estimated rod length, 383 +/- 57 amino acids (0.15 nm/amino acid), implies that globular folding in the BPAG1 N-terminal extends to the end of N-terminal homology with DPI and plectin. These findings support the existence of a common domain structure in the N-terminal regions of the BPAG1/DPI/plectin family (Tang, 1996).

Plectin is a versatile linker protein which is associated with various types of cytoskeletal components and/or filaments including intermediate filaments, and its deficiency causes the disruption of myofibrils, or muscular dystrophy. To better understand the functional role of plectin in skeletal muscle fibers, the topological and structural relationships of plectin to intermediate filaments and Z-discs has been studied in rat diaphragm muscles by confocal and immunoelectron microscopy. Immunofluorescence analysis reveal that plectin is colocalized with desmin at the periphery of Z-discs. This plectin localization around Z-discs is constantly maintained irrespective of the contracted or extended state of the muscle fibers, suggesting either direct or indirect association of plectin with Z-discs. Plectin-labeled fine threads link desmin intermediate filaments to Z-discs and connect intermediate filaments to each other. These results indicate that, through plectin threads, desmin intermediate filaments form lateral linkages among adjacent Z-discs, preventing individual myofibrils from disruptive contraction and ensuring effective force generation (Hijikata, 1999).

Plectin, a versatile cytoskeletal linker protein, has an important role in maintaining the structural integrity of diverse cells and tissues. Plectin (-/-) mice die 2-3 days after birth exhibiting skin blistering caused by degeneration of keratinocytes. Ultrastructurally, hemidesmosomes and desmosomes appear unaffected. In plectin-deficient mice, however, hemidesmosomes are significantly reduced in number and apparently their mechanical stability is altered. The skin phenotype of these mice is similar to that of patients suffering from epidermolysis bullosa simplex (EBS)-MD, a hereditary skin blistering disease with muscular dystrophy, caused by defects in the plectin gene. In addition, plectin (-/-) mice reveal abnormalities reminiscent of minicore myopathies in skeletal muscle and disintegration of intercalated discs in heart. These results clearly demonstrate a general role of plectin in the reinforcement of mechanically stressed cells. Plectin (-/-) mice will provide a useful tool for the study of EBS-MD, and possibly other types of plectin-related myopathies involving skeletal and cardiac muscle, in an organism amenable to genetic manipulation (Andra, 1997).

Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, it was found that their actin cytoskeleton, including focal adhesion contacts, is developed more extensively than in wild-type. Also the actin cytoskeleton fails to show characteristic short-term rearrangments in response to extracellular stimuli activating the Rho/Rac/Cdc42 signaling cascades. As a consequence, cell motility, adherence, and shear stress resistance are altered, and morphogenic processes are delayed. Plectin interacts with G-actin in vitro in a phosphatidylinositol-4,5-biphosphate-dependent manner and associates with actin stress fibers in living cells. The actin stress fiber phenotype of plectin-deficient fibroblasts can be reversed to a large degree by transient transfection of full-length plectin or plectin fragments containing the amino-terminal actin-binding domain (ABD). These results reveal a novel role of plectin as regulator of cellular processes involving actin filament dynamics that goes beyond its proposed role in scaffolding and mechanical stabilization of cells (Andra, 1998).

A full-length cDNA of mouse actin cross-linking family 7 (mACF7) has been cloned by sequential rapid amplification of cDNA ends-PCR. The completed mACF7 cDNA is 17 kb and codes for a 608-kD protein. The closest relative of mACF7 is the Drosophila protein Kakapo, which shares similar architecture with mACF7. mACF7 contains a putative actin-binding domain and a plakin-like domain that are highly homologous to dystonin (BPAG1-n) at its NH(2) terminus. However, unlike dystonin, mACF7 does not contain a coiled-coil rod domain; instead, the rod domain of mACF7 is made up of 23 dystrophin-like spectrin repeats. At its COOH terminus, mACF7 contains two putative EF-hand calcium-binding motifs and a segment homologous to the growth arrest-specific protein, Gas2. The NH(2)-terminal actin-binding domain of mACF7 is functional both in vivo and in vitro. Importantly, the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules. In transfected cells, full-length mACF7 can associate not only with actin but also with microtubules. Hence, a modified name is suggested: MACF (microtubule actin cross-linking factor). The properties of MACF are consistent with the observation that mutations in kakapo cause disorganization of microtubules in epidermal muscle attachment cells and some sensory neurons (Leung, 1999).

Plectin: homologous to the N-terminal domain of Kakapo
(1) Expression in neurons

Typified by rapid degeneration of sensory neurons, dystonia musculorum mice have a defective BPAG1 gene, known to be expressed in epidermis. A neuronal splice form, BPAG1n, is reported which localizes to sensory axons. Both isoforms have a coiled-coil rod, followed by a carboxy domain that associates with intermediate filaments. However, the amino terminus of BPAG1n differs from BPAG1e in that it contains a functional actin-binding domain. In transfected cells, BPAG1n coaligns neurofilaments and microfilaments, establishing this as a cytoskeletal protein interconnecting actin and intermediate filament cytoskeletons. In BPAG1 null mice, axonal architecture is markedly perturbed, consistent with a failure to tether neurofilaments to the actin cytoskeleton and underscoring the physiological relevance of this protein (Yang, 1996).

Ablation of the BPAG1 gene results in the dystonia musculorum mouse, exhibiting rapid spinal nerve degeneration, dystonic movements, and severe ataxia. By defining the developmental and tissue-specific expression of the neuronal form of BPAG1 (BPAG1-n) and by comparing the corresponding pathology in BPAG1 null mice, an attempt has been undertaken to understand how absence of BPAG1 results in this devastating phenotype in mice and in potentially related human neurological disorders. Throughout normal development, BPAG1-n was expressed in a variety of sensory and autonomic neuronal structures, but is absent or reduced in areas such as basal ganglia that are often affected in dystonias and ataxias. Interestingly, BPAG1-n is also expressed broadly in embryonic motor neurons, but expression declined dramatically after birth. Despite these complex developmental patterns, BPAG1-/- pathology is restricted largely to postnatal development. Moreover, gross neuronal degeneration is restricted to only a few regions where BPAG1-n is found, including dorsal root ganglion neurons and a small subset of motor neurons. Most notably, while skeletal muscle is normal, appearance of severe dystonic ataxia correlates with postnatal degeneration of muscle spindles. Collectively, these findings suggest a mechanism for the BPAG1 null phenotype and indicate that different neurons respond differently to the absence of BPAG1-n, a cytoskeletal linker protein (Dowling, 1997).

The mouse neurological mutant dystonia musculorum (dt) suffers from a hereditary sensory neuropathy. The dt gene has been cloned and named dystonin (Dst). Dystonin is a neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin-binding domain. It has been shown previously that dystonin is a cytoskeletal linker protein, forming a bridge between F-actin and intermediate filaments. Two different antibody preparations against dystonin detect a high-molecular-weight protein in immunoblot analysis of spinal cord extracts. This high-molecular-weight protein is not detectable in the nervous system of all dt alleles tested. Immunohistochemical analysis reveals that dystonin is present in different compartments of neurons-cell bodies, dendrites, and axons, regions which are rich in the three elements of the cytoskeleton (F-actin, neurofilaments, and microtubules). Ultrastructural analysis of dt dorsal root axons reveals disorganization of the neurofilament network and surprisingly also of the microtubule network. In this context it is of interest that altered levels of the microtubule-associated proteins MAP2 and tau is observed in spinal cord neurons of different dt alleles. Finally, dt dorsal root ganglion neurons formed neurites in culture, but the cytoskeleton is disorganized within these neurites. These results demonstrate that dystonin is essential for maintaining neuronal cytoskeleton integrity but is not required for establishing neuronal morphology (Dalpe, 1999).

Plectin: homologous to the N-terminal domain of Kakapo
(2) Localization to junctions and connection with microtubules

continued at kakapo Evolutionary homologs part 2/2

kakapo: Biological Overview | Regulation | Developmental Biology | Effects of Mutation | References

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