InteractiveFly: GeneBrief

CAP: Biological Overview | References

Gene name - CAP

Synonyms - Cbl-associated protein

Cytological map position 46F9-47A1

Function - signaling

Keywords - muscle attachment sites, scolopale cells, chordotonal organs, stretch-sensitive organ assembly and function, Johnston's organ, glucose transport

Symbol - CAP

FlyBase ID: FBgn0033504

Genetic map position - chr2R:6,156,582-6,194,713

Classification - vinexin family

Cellular location - cytoplasmic

NCBI link: EntrezGene

CAP orthologs: Biolitmine
Recent literature
Jammrath, J., Reim, I. and Saumweber, H. (2020). Cbl-Associated Protein CAP contributes to correct formation and robust function of the Drosophila heart tube. PLoS One 15(5): e0233719. PubMed ID: 32469960
In Drosophila, the cardiac tube originates from two bilateral rows of dorsally migrating cells. On meeting at the dorsal midline, coordinated changes in cell shape and adhesive properties transform the two sheets of cells into a linear tube. This study characterized the requirement of Cbl-Associated Protein (CAP) in Drosophila heart formation. In embryos, CAP is expressed in late migrating cardioblasts and is located preferentially at their luminal and abluminal periphery. CAP mutations result in irregular cardioblast alignment and imprecisely controlled cardioblast numbers. Furthermore, CAP mutant embryos show a strongly reduced heart lumen and an aberrant shape of lumen forming cardioblasts. Analysis of double heterozygous animals reveals a genetic interaction of CAP with Integrin- and Talin-encoding genes. In post-embryonic stages, CAP closely colocalizes with Integrin near Z-bands and at cell-cell contact sites. CAP mutants exhibit a reduced contractility in larval hearts and show a locally disrupted morphology, which correlates with a reduced pumping efficiency. These observations imply a function of CAP in linking Integrin signaling with the actin cytoskeleton.
Dondi, C., Bertin, B., Daponte, J. P., Wojtowicz, I., Jagla, K. and Junion, G. (2021). A polarized nucleus-cytoskeleton-ECM connection in migrating cardioblasts controls heart tube formation. Development. PubMed ID: 34228803
The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. This study identified CAP and MSP300 as novel actors involved during CBs migration. They both exhibit highly similar temporal and spatial expression patterns in migrating cardiac cells and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. These data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.

Cbl-associated protein (CAP) localizes to focal adhesions and associates with numerous cytoskeletal proteins; however, its physiological roles remain unknown. This study demonstrates that Drosophila CAP regulates the organization of two actin-rich structures in Drosophila: muscle attachment sites (MASs), which connect somatic muscles to the body wall; and scolopale cells, which form an integral component of the fly chordotonal organs and mediate mechanosensation. Drosophila CAP mutants exhibit aberrant junctional invaginations and perturbation of the cytoskeletal organization at the MAS. CAP depletion also results in collapse of scolopale cells within chordotonal organs, leading to deficits in larval vibration sensation and adult hearing. This study investigated the roles of different CAP protein domains in its recruitment to, and function at, various muscle subcellular compartments. Depletion of the CAP-interacting protein Vinculin results in a marked reduction in CAP levels at MASs, and vinculin mutants partially phenocopy Drosophila CAP mutants. These results show that CAP regulates junctional membrane and cytoskeletal organization at the membrane-cytoskeletal interface of stretch-sensitive structures, and they implicate integrin signaling through a CAP/Vinculin protein complex in stretch-sensitive organ assembly and function (Bharadwaj, 2013).

Interactions between cells and the extracellular matrix (ECM) are crucial for many biological processes. These include cell migration, directed process outgrowth, basement membrane-mediated support of tissues and maintenance of cell shape. Communication between cells and ECM proteins often occurs through the action of α/β-integrin heterodimers, a receptor complex that forms adhesive contacts, including focal adhesions, hemiadherens junctions, costameres and myotendinous junctions. In response to extracellular forces, focal adhesions undergo structural changes and initiate signaling events that allow adaptation to tensile stress. Vinculin is thought to be the primary force sensor in the integrin complex, mediating homeostatic adaptation to external forces (Carisey, 2011; Grashoff, 2010; Hytönen, 2008; Bharadwaj, 2013 and references therein).

Vinculin-binding partners include proteins belonging to the CAP (Cbl-associated protein) protein family (Kioka, 1999). However, the physiological significance of this association is unknown. Mammalian CAP proteins are components of focal adhesions in cell culture (Kioka, 1999; Zhang, 2006). In myocytes, CAP localizes to integrin-containing complexes called costameres that anchor sarcomeres to muscle cell membranes (Zhang, 2007). There are three mammalian CAP protein family members: CAP, Vinexin and ArgBP2 (Kioka, 2002). CAP associates in vitro with many proteins, including the cytoskeletal regulators Paxillin, Afadin and Filamin, vesicle trafficking regulators such as Dynamin and Cbl, and the lipid raft protein Flotillin (Chiang, 2001; Mandai, 1999; Zhang, 2006; Zhang, 2007). In vitro studies demonstrate that CAP regulates the reassembly of focal adhesions following nocodazole dissolution (Zhang, 2006). However, despite extensive studies on CAP (Kioka, 2002; Zhang, 2006), little is known about its functions in vivo. Cap (Sorbs1) mutant mice are defective in fat metabolism, and targeted deletion of the vinexin gene results in wound-healing defects (Kioka, 2010; Lesniewski, 2007). Drosophila CAP binds to axin and is implicated in glucose metabolism (Yamazaki, 2002; Yamazaki, 2003). Analysis of CAP function in mammals is complicated by potential functional redundancy of the three related CAP proteins. Therefore, the function of Drosophila CAP, the single CAP family member in Drosophila, was examined in vivo (Bharadwaj, 2013).

The Drosophila muscle attachment site (MAS) is an excellent system for studying integrin signaling. Somatic muscles in each segment of the fly embryo and larva are connected to the body wall through integrin-mediated hemiadherens junctions. Somatic muscles in flies lacking integrins lose their connection to the body wall. Surprisingly, flies lacking Vinculin, a major component of cytosolic integrin signaling complexes, are viable and show no muscle defects (Alatortsev, 1997). Thus, unlike its mammalian counterpart, Drosophila Vinculin is apparently dispensable for the initial assembly of integrin-mediated adhesion complexes at somatic MASs (Bharadwaj, 2013).

The fly MAS is structurally analogous to the fly chordotonal organ. These organs transduce sensations from various stimuli, including vibration, sound, gravity, airflow and body wall movements. The chordotonal organ is composed of individual subunits called scolopidia, each containing six cell types: neuron, scolopale, cap, ligament, cap attachment and ligament attachment cells (Todi, 2004). Chordotonal neurons are monodendritic, and their dendrites are located in the scolopale space, a lymph-filled extracellular space completely enveloped by the scolopale cell (Todi, 2004). Within the scolopale cell, a cage composed of actin bars, called scolopale rods, facilitates scolopale cell envelopment of the scolopale space (Todi, 2004). Thus, like the MAS, the actin cytoskeleton plays a specialized role in defining chordotonal organ morphology. Similarities between MASs and chordotonal organs include the requirement during development in both tendon and cap cells for the transcription factor Stripe. Furthermore, both of these cell types maintain structural integrity under force and so are likely to share common molecular components dedicated to this function (Bharadwaj, 2013).

This study shows that the Drosophila CAP protein is selectively localized to both muscle attachment sites and chordotonal organs. In Drosophila CAP mutants morphological defects are observed that are indicative of actin disorganization in both larval MASs and the scolopale cells of Johnston's organ in the adult. The morphological defects in scolopale cells result in vibration sensation defects in larvae and hearing deficits in adults. It was also found that, like its mammalian homologues, Drosophila CAP interacts with Vinculin both in vitro and in vivo. These results reveal novel CAP functions required for actin-mediated organization of cellular morphology, lending insight into how CAP mediates muscle and sensory organ development and function (Bharadwaj, 2013).

Integrin-based adhesion complexes are crucial for cell attachment to the extracellular matrix. These complexes change their composition and architecture in response to extracellular forces, initiating downstream signaling events that regulate cytoskeletal organization (Geiger, 2009). This study has investigated the role played by the CAP protein in two stretch-sensitive structures in Drosophila: the MAS and the chordotonal organ. CAP mutants exhibit aberrant junctional invaginations at the MAS and collapse of scolopale cells in chordotonal organs. This study highlights a crucial integrin signaling function during development: the maintenance of membrane morphology in stretch-sensitive structures (Bharadwaj, 2013).

The morphological defects observed in CAP mutants could result from an excessive integrin signaling, or possibly accumulation of additional membranous components related to integrin signaling, in CAP mutants, owing to defects in endocytosis at the MAS. This is consistent with known interactions between CAP family members and vesicle trafficking regulators, including Dynamin and Synaptojanin, which are required for internalization of transmembrane proteins (Cestra, 2005; Tosoni, 2009). Alternatively, CAP may be required for proper organization of the actin cytoskeleton at MASs, and the aberrant membrane invaginations that were observe are a secondary consequence of these cytoskeletal defects. This idea garners support from known interactions between CAP and various actin-binding proteins, including Vinculin, Paxillin, Actinin, Filamin and WAVE2 (Cestra, 2005; Kioka, 2002; Kioka, 2002; Zhang, 2006). A third possibility is that CAP and Vinculin are regulators of membrane stiffness at the MAS, and aberrant junctional infoldings observed in CAP and vinculin mutants derive from diminished membrane rigidity in the presence of persistent myofilament contractile forces. Biophysical studies demonstrate that Vinculin-deficient mammalian cells in vitro show reduced membrane stiffness. Interestingly, the CAP protein ArgBP2 interacts with Spectrin, a protein important for cell membrane rigidity maintenance (Cestra, 2005). These models for CAP function at MASs, however, are not mutually exclusive. Interestingly, disruption of the ECM protein Tiggrin leads to MAS phenotypes similar to CAP. Future studies on CAP interaction with Tiggrin and other CAP-interacting proteins will shed light on mechanisms underlying CAP function. Nevertheless, this study demonstrates in vivo the importance of CAP in stretch-sensitive organ morphogenesis, and it will be interesting to determine whether this function is phylogenetically conserved (Bharadwaj, 2013).

Apart from the MAS, CAP is also expressed at high levels in chordotonal organ scolopale cells, and this study has found that CAP mutants are defective in vibration sensation, a hallmark of chordotonal organ dysfunction. However, only the initial fast hunching response to vibration is disrupted in CAP mutant larvae. This may result from a partial loss of chordotonal function in these organs in the absence of CAP. A functional defect was also observed in the adult Johnston's organ; CAP mutant flies show diminished sound-evoked potentials. Importantly, the scolopale cells in CAP mutants appear partially collapsed. The extracellular space within the scolopale cell is lined by an actin cage, and CAP may influence the proper assembly of this actin cage or its association with the scolopale cell membrane. Ch organs are mechanosensory detectors and are constantly exposed to tensile forces. Thus, CAP apparently influences cytoskeletal integrity in two actin-rich structures: the MAS and the chordotonal organ, both of which are involved in force transduction (Bharadwaj, 2013).

Mammalian and Drosophila CAP bind to Vinculin (Kioka, 2002; Kioka, 2002; Zhang, 2006). Vinculin is required for the recruitment of the mammalian CAP protein vinexin to focal adhesions in NIH3T3 cells in vitro (Takahashi, 2005). Consistent with this observation, a dramatic decrease was seen in CAP levels at MASs in vinculin mutants, but residual levels of CAP protein remain. Furthermore, CAP localization at the muscle fiber Z-lines is completely unaltered in vinculin mutants. These observations indicate that Vinculin is not the sole upstream regulator of CAP localization. vinculin mutants show some of the phenotypic defects observed in CAP mutants; however, these defects are less pronounced. Therefore, the residual CAP pool that is recruited to MASs in a Vinculin-independent manner is apparently sufficient for partial CAP function. Assessment of CAP and Vinculin function at the larval MAS shows that these proteins are required for maintaining the integrity of junctional membranes in the face of tensile forces. CAP proteins may serve as scaffolding proteins at membrane-cytoskeleton interfaces and facilitate the assembly of protein complexes involved in cytoskeletal regulation and membrane turnover (Bharadwaj, 2013).

Mutations in the CAP-binding protein filamin cause myofibrillar myopathy. This, in combination with data showing a crucial role for CAP in regulation of muscle morphology, sets the stage for investigating how loss of CAP protein function might influence the etiology of myopathies (Bharadwaj, 2013).

Identification of CAP as a costameric protein that interacts with filamin C

Cbl-associated protein (CAP) is an adaptor protein that interacts with both signaling and cytoskeletal proteins. This study characterized the expression, localization and potential function of CAP in mammalian striated muscle. CAP is markedly induced during myoblast differentiation, and colocalizes with vinculin during costamerogenesis. In adult mice, CAP is enriched in oxidative muscle fibers, and it is found in membrane anchorage complexes, including intercalated discs, costameres, and myotendinous junctions. Using both yeast two-hybrid and proteomic approaches, the sarcomeric protein filamin C (FLNc) was identified as a binding partner for CAP. When overexpressed, CAP recruits FLNc to cell-extracellular matrix adhesions, where the two proteins cooperatively regulate actin reorganization. Moreover, overexpression of CAP inhibits FLNc-induced cell spreading on fibronectin. In dystrophin-deficient mdx mice, the expression and membrane localization of CAP is increased, concomitant with the elevated plasma membrane content of FLNc, suggesting that CAP may compensate for the reduced membrane linkage of the myofibrils due to the loss of the dystroglycan-sarcoglycan complex in these mice. Thus, through its interaction with FLNc, CAP provides another link between the myofibril cytoskeleton and the plasma membrane of muscle cells, and it may play a dynamic role in the regulation and maintenance of muscle structural integrity (Zhang, 2007).

Axin and the Axin/Arrow-binding protein DCAP mediate glucose-glycogen metabolism

Axin was found as a negative regulator of the canonical Wnt pathway. Human LRP5 was originally found as a candidate gene of insulin dependent diabetes mellitus (IDDM), but its Drosophila homolog, Arrow, works as a co-receptor of the canonical Wnt signal. A previous paper described Drosophila Axin (Daxin)-binding SH3 protein, DCAP, a homolog of mammalian CAV family protein (Yamazaki, 2002). Among the subtypes, DCAPL3 shows significant homology with CAP, an essential component of glucose transport in insulin signal. Further binding assay revealed that DCAP binds to not only Axin but also Arrow, and Axin binds to not only GSK3beta but also Arrow. However, overexpression and RNAi experiments of DCAP do not affect the canonical Wnt pathway. As DCAP is expressed predominantly in insulin-target organs, and as RNAi of DCAP disrupts the pattern of endogenous glycogen accumulation in late stage embryos, it is suggested that DCAP is also involved in glucose transport. Moreover, early stage embryos lacking maternal Axin show significant delay of initial glycogen decomposition, and RNAi of Axin in S2 cells revealed quite increase of endogenous glycogen level as well as GSK3beta. These results suggest that Axin and DCAP mediate glucose-glycogen metabolism in embryo. In addition, the interaction among Axin, Arrow, and DCAP implies a possible cross-talk between Wnt signal and insulin signal (Yamazaki, 2003).

This study shows that DCAP binds to not only Axin but also the cytoplasmic tail of Arrow through SH3 domains. Usually, SH3 proteins mediate protein-protein interaction in signal transduction and often link different pathways for cross talking of signals. Therefore, it is possible that DCAP can connect Wnt signaling molecules to other pathways. Although it could not be proven that DCAP participates in the canonical Wnt pathway, it was shown that DCAP is also a functional homolog of mammalian CAP in insulin signal and controls proper localization of endogenous glycogen in late stage embryos. These results suggest that the glucose transport by DCAP can be affected by Wnt signaling molecules (Yamazaki, 2003).

In the case of Axin, it binds to GSK3β, a glucose-glycogen metabolism-modifying enzyme, and also binds to DCAP, one of the components for insulin-dependent glucose transport. Novel glycogen phenotypes were found in D-axin null mutants and DCAP-RNAi embryos. In addition, RNAi of Axin in S2 increases the level of endogenous glycogen. These findings mean that Axin controls glycogen level as well as GSK3β, and this function is thought to be another important function of Axin as well as inhibiting the canonical Wnt signal (Yamazaki, 2003).

The binding between DCAP and Arrow is also quite intriguing. Arrow is a coreceptor of the canonical Wnt pathway in Drosophila. However, its human homolog LRP5 was originally identified as a candidate gene for IDDM4. Axin binds to not only GSK3β and DCAP but also Arrow/LRP5. Therefore, it is also possible that Axin, Arrow, GSK3β, and DCAP work together in glucose-glycogen metabolism or insulin signal (Yamazaki, 2003).

Although LRP5 is well studied in the canonical Wnt pathway, the function in insulin signal still needs to be investigated further. In a previous report, LRP5 was shown to be expressed in β cells of pancreatic Langerhans islets. The disruption of LRP5 can inhibit glucose uptake into β cells and cause Insulin-Dependent Diabetes Mellitus (IDDM), because β cells would misjudge blood glucose as low levels and would not release insulin. Mammalian CAP is also supposed to interact with LRP5, so this interaction may give significant insights in IDDM (Yamazaki, 2003).

Moreover, recent works revealed that Drosophila insulin signal controls cell size and number in late stage embryo during development. It is after the initial canonical Wnt signal but the same period as DCAP expression. This means that insulin signal has another function other than controlling blood glucose level. Therefore, it is considered that Wnt signal and insulin signal molecules interact each other for development other than the canonical Wnt pathway or controlling blood glucose (Yamazaki, 2003).

Until now, several cross talks have been reported in Wnt signal. As GSK3β and Arrow are already known to be multifunctional molecules, it is quite reasonable that Axin is another bifunctional molecule both in Wnt signal and glucose-glycogen metabolism. Taking together these data, it is also reasonable to think that Wnt signal has a cross-talk with insulin signal. However, the role of Axin in the initial glycogen decomposition is still unclear. It is also unknown why DCAP has five different spliced forms. To study these questions will give significant insights into the signaling network of development (Yamazaki, 2003).

Identification of DCAP, a Drosophila homolog of a glucose transport regulatory complex

In a yeast two-hybrid screen using the Drosophila Axin protein as a bait, a Drosophila homolog of CAP, a component of the glucose transport regulatory complex was identifed. Through alternative splicing, the DCAP gene generates a set of five different proteins with unique N-terminal sequences and a common C-terminal SH3 domain. DCAP is predominantly expressed in the midgut and fat bodies of late-stage embryos, suggesting a role in insulin-mediated glucose transport in these organs (Yamazaki, 2002).

In Drosophila, the Wingless (Wg) signal is transduced through the Frizzled and Arrow (LRP) receptors, Dishevelled, Zw3 (GSK3β) and Axin to activate the Armadillo (or β-catenin) molecule. Many of the Wg signal transduction components are dedicated to this pathway, but there are also cases of proteins that work in other systems as well: the GSK3 (glycogen synthase kinase 3) enzyme is also involved in glucose metabolism, for example. This work provides evidence that Axin can interact with another protein involved in glucose metabolism, the CAP protein (Yamazaki, 2002).

A yeast two-hybrid screen was carried out using an expression library made from Drosophila embryo RNA and Drosophila Axin as a bait, and a protein containing three SH3 domains in the C-terminus was identified. This gene was mapped to the second chromosome 46F9 to 47A1. A full-length cDNA of this gene was cloned from embryonic Drosophila libraries. The gene generates five types of mRNAs encoding proteins with distinct N-terminal sequences, generated by alternative splicing. These spliced forms were named L1 (2376aa), L2 (1743aa), L3 (824aa), L4 (527aa), and S (313aa). The various N-terminal sequences have no homology with each other, but several proline-rich domains are found in each N-terminus (Yamazaki, 2002).

Homologous proteins were sought in other species, and L3 was found to have considerable homology with the mammalian CAV family proteins, CAP/Ponsin, ArgBP2, and Vinexin. The N-terminal sequences of these proteins have low homology, but all of them have a sorbin-like domain in the N-terminus and three SH3 domains in the C-terminus. Because of the similarity to mammalian CAP, the Drosophila protein was named DCAP (Yamazaki, 2002).

However, other forms of DCAP have no homology with any proteins or the CAV family except for the SH3 domain. Moreover, DCAPL3 is the only CAV family member in Drosophila genome. Originally, mammalian CAV family proteins were found as proto-oncogene binding proteins and they associate with the actin cytoskeleton, having various functions in cell signaling. Among the CAV family proteins, CAP has been reported to be involved in insulin-stimulated glucose transport (Yamazaki, 2002 and references therein).

The expression pattern of DCAP was examined by Northern blotting using the common SH3 domains as a probe. The main transcripts of DCAP are 3, 6, and 9 kb, and appear from 10 h after egg laying (AEL). Judging from subtype-specific Northern blots, the 9 and 6 kb bands correspond to DCAPL1, L2, respectively, and the 3 kb band corresponds to L3, L4 and S. Anti-DCAP antibodies (against the common SH3 domains) was generated, and the time courses of DCAP expression was determined in the embryo. DCAP protein is detected as five different molecular weight bands, and the expression is first detectable 13 h AEL with a gradual increase (Yamazaki, 2002).

To verify the binding between Axin and DCAP, various constructs were made with glutathione-S-transferase (GST) or poly Histidine-tags (His-tag). Daxin has three proline-rich domains (PRD) consensus sequences (PXXP motif, amino acids (aa), 315, 525, and, 612), known to be a binding motif of SH3 domains. Confirming the two-hybrid data, DCAP binds to Axin. It was also found that the N-terminus of DCAPL3 binds to its own SH3 domains, suggesting an intramolecular interaction between the SH3-PRD, and the SH3 domains of DCAP (Yamazaki, 2002).

The localization of DCAP was examined by in-situ hybridization. DCAP was found to be predominantly expressed in midgut and fat bodies in late-stage embryos. These organs consist of insulin response cells such as muscle cells or adipocytes, respectively (Yamazaki, 2002).

To further examine the relation between DCAP expression and glucose metabolism, a periodic acid Schiff (PAS) staining method was establised in Drosophila embryos to detect endogenous glycogen. Glycogen is abundant in eggs and early embryos, presumably coming from maternal sources. However, as development proceeds, glycogen is metabolized and levels become low before gastrulation. These low levels are maintained during middle stages (3-10 h AEL, stages 5-14). Then glycogen begins to accumulate in the midgut (stage 15-), and spreads all over the embryo until hatching. It is interesting to note that the secondary accumulation of glycogen coincides with expression of DCAP in the midgut and the fatbody. Further work will be required to address the function of this DCAP in Drosophila development (Yamazaki, 2002).


Search PubMed for articles about CAP

Alatortsev, V. E., Kramerova, I. A., Frolov, M. V., Lavrov, S. A. and Westphal, E. D. (1997). Vinculin gene is non-essential in Drosophila melanogaster. FEBS Lett 413: 197-201. PubMed ID: 9280281

Bharadwaj, R., Roy, M., Ohyama, T., Sivan-Loukianova, E., Delannoy, M., Lloyd, T. E., Zlatic, M., Eberl, D. F. and Kolodkin, A. L. (2013). Cbl-associated protein regulates assembly and function of two tension-sensing structures in Drosophila. Development 140: 627-638. PubMed ID: 23293294

Carisey, A. and Ballestrem, C. (2011). Vinculin, an adapter protein in control of cell adhesion signalling. Eur J Cell Biol 90: 157-163. PubMed ID: 20655620

Cestra, G., Toomre, D., Chang, S. and De Camilli, P. (2005). The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton. Proc Natl Acad Sci U S A 102: 1731-1736. PubMed ID: 15659545

Chiang, S. H., Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L., Macara, I. G., Pessin, J. E. and Saltiel, A. R. (2001). Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410: 944-948. PubMed ID: 11309621

Geiger, B., Spatz, J. P. and Bershadsky, A. D. (2009). Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10: 21-33. PubMed ID: 19197329

Grashoff, C., Hoffman, B. D., Brenner, M. D., Zhou, R., Parsons, M., Yang, M. T., McLean, M. A., Sligar, S. G., Chen, C. S., Ha, T. and Schwartz, M. A. (2010). Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466: 263-266. PubMed ID: 20613844

Hytonen, V. P. and Vogel, V. (2008). How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism. PLoS Comput Biol 4: e24. PubMed ID: 18282082

Kioka, N., Sakata, S., Kawauchi, T., Amachi, T., Akiyama, S. K., Okazaki, K., Yaen, C., Yamada, K. M. and Aota, S. (1999). Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. J Cell Biol 144: 59-69. PubMed ID: 9885244

Kioka, N., Ueda, K. and Amachi, T. (2002). Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell Struct Funct 27: 1-7. PubMed ID: 11937713

Kioka, N., Ito, T., Yamashita, H., Uekawa, N., Umemoto, T., Motoyoshi, S., Imai, H., Takahashi, K., Watanabe, H., Yamada, M. and Ueda, K. (2010). Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo. Exp Cell Res 316: 1728-1738. PubMed ID: 20361963

Lesniewski, L. A., Hosch, S. E., Neels, J. G., de Luca, C., Pashmforoush, M., Lumeng, C. N., Chiang, S. H., Scadeng, M., Saltiel, A. R. and Olefsky, J. M. (2007). Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance. Nat Med 13: 455-462. PubMed ID: 17351624

Mandai, K., Nakanishi, H., Satoh, A., Takahashi, K., Satoh, K., Nishioka, H., Mizoguchi, A. and Takai, Y. (1999). Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. J Cell Biol 144: 1001-1017. PubMed ID: 10085297

Takahashi, H., Mitsushima, M., Okada, N., Ito, T., Aizawa, S., Akahane, R., Umemoto, T., Ueda, K. and Kioka, N. (2005). Role of interaction with vinculin in recruitment of vinexins to focal adhesions. Biochem Biophys Res Commun 336: 239-246. PubMed ID: 16126177

Todi, S. V., Sharma, Y. and Eberl, D. F. (2004). Anatomical and molecular design of the Drosophila antenna as a flagellar auditory organ. Microsc Res Tech 63: 388-399. PubMed ID: 15252880

Tosoni, D. and Cestra, G. (2009). CAP (Cbl associated protein) regulates receptor-mediated endocytosis. FEBS Lett 583: 293-300. PubMed ID: 19116150

Yamazaki, H. and Nusse, R. (2002). Identification of DCAP, a Drosophila homolog of a glucose transport regulatory complex. Mech Dev 119: 115-119. PubMed ID: 12385759

Yamazaki, H. and Yanagawa, S. (2003). Axin and the Axin/Arrow-binding protein DCAP mediate glucose-glycogen metabolism. Biochem Biophys Res Commun 304: 229-235. PubMed ID: 12711303

Zhang, M., Liu, J., Cheng, A., Deyoung, S. M., Chen, X., Dold, L. H. and Saltiel, A. R. (2006). CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility. EMBO J 25: 5284-5293. PubMed ID: 17082770

Zhang, M., Liu, J., Cheng, A., Deyoung, S. M. and Saltiel, A. R. (2007). Identification of CAP as a costameric protein that interacts with filamin C. Mol Biol Cell 18: 4731-4740. PubMed ID: 17898075

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date revised: 22 June 2013

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