{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:01:08Z","timestamp":1791273668945,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1,15]]},"abstract":"<jats:p>The formation and extension of filopodia in response to an extracellular stimulus by guidance cues determine the path of growth cone advance. Actin-filament bundling and actin polymerization at the tips supply the driving force behind the formation and elongation. We tried to clarify how signals in response to extracellular cues are transformed to induce filopodial generation and extension. Observations on the formation process of filopodia at growth cones in the neuroblastoma cell line NG108 showed that WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin homologous protein) isoforms played crucial and distinct roles in this process. WAVE1 was continuously distributed along the leading edge only and was not found in the filopodia. WAVE2 and WAVE3 discretely localized at the initiation sites of microspikes on the leading edge and also concentrated at the tips of protruding filopodia. We further found that WAVE isoforms localized at the filopodial tips through SHD (SCAR homology domain), next to its leucine zipper-like motif. Furthermore, time-lapse observations of filopodial formation in living cells showed that WAVE2 and WAVE3 were continuously expressed at the tips of filopodia during elongation. These results indicate that WAVE2 or WAVE3 may guide the actin bundles into the filopodia and promote actin assembly at the tips.<\/jats:p>","DOI":"10.1242\/jcs.00233","type":"journal-article","created":{"date-parts":[[2002,12,13]],"date-time":"2002-12-13T13:22:55Z","timestamp":1039785775000},"page":"239-246","source":"Crossref","is-referenced-by-count":80,"title":["Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone"],"prefix":"10.1242","volume":"116","author":[{"given":"Motohiro","family":"Nozumi","sequence":"first","affiliation":[{"name":"Department of Biochemical Science, Kyushu Institute of Technology, 680-4 Kawatsu, lizuka, Fukuoka 820-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science, Kyushu Institute of Technology, 680-4 Kawatsu, lizuka, Fukuoka 820-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaomi","family":"Takenawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science, Kyushu Institute of Technology, 680-4 Kawatsu, lizuka, Fukuoka 820-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042517455044100_REF1","doi-asserted-by":"crossref","unstructured":"Bear, J. E., Svitkina, T. M., Krause, M., Schafer, D. A., Loureiro, J. J., Strasser, G. A., Maly, I. V., Chaga, O. Y., Cooper, J. A., Borisy, G. G. et al. (2002). Antagonism between Ena\/VASP proteins and actin filament capping regulates fibroblast motility. Cell109, 509-521.","DOI":"10.1016\/S0092-8674(02)00731-6"},{"key":"2021042517455044100_REF2","doi-asserted-by":"crossref","unstructured":"Bentley, D. and O'Connor, T. P. (1994). Cytoskeletal events in growth cone steering. Curr. Opin. Neurobiol.4, 43-48.","DOI":"10.1016\/0959-4388(94)90030-2"},{"key":"2021042517455044100_REF3","doi-asserted-by":"crossref","unstructured":"Borisy, G. G. and Svitkina, T. M. (2000). Actin machinery: pushing the envelope. Curr. Opin. Cell Biol.12, 104-112.","DOI":"10.1016\/S0955-0674(99)00063-0"},{"key":"2021042517455044100_REF4","doi-asserted-by":"crossref","unstructured":"Cohan, C. S., Welnhofer, E. A., Zhao, L., Matsumura, F. and Yamashiro, S. (2001). Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia. Cell Motil. Cytoskeleton48, 109-120.","DOI":"10.1002\/1097-0169(200102)48:2<109::AID-CM1002>3.0.CO;2-G"},{"key":"2021042517455044100_REF5","doi-asserted-by":"crossref","unstructured":"Eden, S., Rohatgi, R., Podtelejnikov, A. V., Mann, M. and Kirschner, M. W. (2002). Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature418, 790-793.","DOI":"10.1038\/nature00859"},{"key":"2021042517455044100_REF6","doi-asserted-by":"crossref","unstructured":"Furuya, S. and Furuya, K. (1983). Ultrastructural changes in differentiating neuroblastoma x glioma hybrid cells. Tissue Cell15, 903-919.","DOI":"10.1016\/0040-8166(83)90057-5"},{"key":"2021042517455044100_REF7","doi-asserted-by":"crossref","unstructured":"Govind, S., Kozma, R., Monfries, C., Lim, L. and Ahmed, S. (2001). Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin. J. Cell Biol.152, 579-594.","DOI":"10.1083\/jcb.152.3.579"},{"key":"2021042517455044100_REF8","doi-asserted-by":"crossref","unstructured":"Hahne, P., Sechi, A., Benesch, S. and Small, J. V. (2001). Scar\/WAVE is localised at the tips of protruding lamellipodia in living cells. FEBS Lett.492, 215-220.","DOI":"10.1016\/S0014-5793(01)02239-6"},{"key":"2021042517455044100_REF9","doi-asserted-by":"crossref","unstructured":"Hall, A. (1998). Rho GTPases and the actin cytoskeleton. Science279, 509-514.","DOI":"10.1126\/science.279.5350.509"},{"key":"2021042517455044100_REF10","unstructured":"Heath, J. P. and Holifield, B. F. (1993). On the mechanisms of cortical actin flow and its role in cytoskeletal organisation of fibroblasts. Symp. Soc. Exp. Biol.47, 35-56."},{"key":"2021042517455044100_REF11","doi-asserted-by":"crossref","unstructured":"Katoh, K., Hammar, K., Smith, P. J. and Oldenbourg, R. (1999a). Birefringence imaging directly reveals architectural dynamics of filamentous actin in living growth cones. Mol. Biol. Cell10, 197-210.","DOI":"10.1091\/mbc.10.1.197"},{"key":"2021042517455044100_REF12","doi-asserted-by":"crossref","unstructured":"Katoh, K., Hammar, K., Smith, P. J. and Oldenbourg, R. (1999b). Arrangement of radial actin bundles in the growth cone of Aplysia bag cell neurons shows the immediate past history of filopodial behavior. Proc. Natl. Acad. Sci. USA96, 7928-7931.","DOI":"10.1073\/pnas.96.14.7928"},{"key":"2021042517455044100_REF13","doi-asserted-by":"crossref","unstructured":"Kim, M. D., Kolodziej, P. and Chiba, A. (2002). Growth cone pathfinding and filopodial dynamics are mediated separately by Cdc42 activation. J. Neurosci.22, 1794-1806.","DOI":"10.1523\/JNEUROSCI.22-05-01794.2002"},{"key":"2021042517455044100_REF14","doi-asserted-by":"crossref","unstructured":"Kirschner, M. W. (1980). Implications of treadmilling for the stability and polarity of actin and tubulin polymers in vivo. J. Cell Biol.86, 330-334.","DOI":"10.1083\/jcb.86.1.330"},{"key":"2021042517455044100_REF15","doi-asserted-by":"crossref","unstructured":"Lanier, L. M. and Gertler, F. B. (2000). From Abl to actin: Abl tyrosine kinase and associated proteins in growth cone motility. Curr. Opin. Neurobiol.10, 80-87.","DOI":"10.1016\/S0959-4388(99)00058-6"},{"key":"2021042517455044100_REF16","doi-asserted-by":"crossref","unstructured":"Lanier, L. M., Gates, M. A., Witke, W., Menzies, A. S., Wehman, A. M., Macklis, J. D., Kwiatkowski, D., Soriano, P. and Gertler, F. B. (1999). Mena is required for neurulation and commissure formation. Neuron22, 313-325.","DOI":"10.1016\/S0896-6273(00)81092-2"},{"key":"2021042517455044100_REF17","doi-asserted-by":"crossref","unstructured":"Lewis, A. K. and Bridgman, P. C. (1992). Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity. J. Cell Biol.119, 1219-1243.","DOI":"10.1083\/jcb.119.5.1219"},{"key":"2021042517455044100_REF18","doi-asserted-by":"crossref","unstructured":"Li, Z., Aizenman, C. D. and Cline, H. T. (2002). Regulation of rho GTPases by crosstalk and neuronal activity in vivo. Neuron33, 741-750.","DOI":"10.1016\/S0896-6273(02)00621-9"},{"key":"2021042517455044100_REF19","doi-asserted-by":"crossref","unstructured":"Lommel, S., Benesch, S., Rottner, K., Franz, T., Wehland, J. and Kuhn, R. (2001). Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells. EMBO Rep.2, 850-870.","DOI":"10.1093\/embo-reports\/kve197"},{"key":"2021042517455044100_","doi-asserted-by":"crossref","unstructured":"Mallavarapu, A. and Mitchison, T. (1999). Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J. Cell Biol.146, 1097-1106.","DOI":"10.1083\/jcb.146.5.1097"},{"key":"2021042517455044100_REF21","doi-asserted-by":"crossref","unstructured":"Miki, H., Suetsugu, S. and Takenawa, T. (1998). WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J.17, 6932-6941.","DOI":"10.1093\/emboj\/17.23.6932"},{"key":"2021042517455044100_REF22","doi-asserted-by":"crossref","unstructured":"Miki, H., Fukuda, M., Nishida, E. and Takenawa, T. (1999). Phosphorylation of WAVE downstream of mitogen-activated protein kinase signaling. J. Biol. Chem.274, 27605-27609.","DOI":"10.1074\/jbc.274.39.27605"},{"key":"2021042517455044100_REF23","doi-asserted-by":"crossref","unstructured":"Miki, H., Yamaguchi, H., Suetsugu, S. and Takenawa, T. (2000). IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature408, 732-735.","DOI":"10.1038\/35047107"},{"key":"2021042517455044100_REF24","doi-asserted-by":"crossref","unstructured":"Mogilner, A. and Oster, G. (1996). Cell motility driven by actin polymerization. Biophys. J.71, 3030-3045.","DOI":"10.1016\/S0006-3495(96)79496-1"},{"key":"2021042517455044100_REF25","doi-asserted-by":"crossref","unstructured":"Nakagawa, H., Yoshida, M. and Miyamoto, S. (2000). Nitric oxide underlies the differentiation of PC12 cells induced by depolarization with high KCl. J. Biochem.127, 113-119.","DOI":"10.1093\/oxfordjournals.jbchem.a022571"},{"key":"2021042517455044100_REF26","doi-asserted-by":"crossref","unstructured":"Nakagawa, H., Miki, H., Ito, M., Ohashi, K., Takenawa, T. and Miyamoto, S. (2001). N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia. J. Cell Sci.114, 1555-1565.","DOI":"10.1242\/jcs.114.8.1555"},{"key":"2021042517455044100_REF27","doi-asserted-by":"crossref","unstructured":"Nikolic, M. (2002). The role of Rho GTPases and associated kinases in regulating neurite outgrowth. Int. J. Biochem. Cell Biol.34, 731-745.","DOI":"10.1016\/S1357-2725(01)00167-4"},{"key":"2021042517455044100_REF28","doi-asserted-by":"crossref","unstructured":"Nobes, C. D. and Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell81, 53-62.","DOI":"10.1016\/0092-8674(95)90370-4"},{"key":"2021042517455044100_REF29","doi-asserted-by":"crossref","unstructured":"Oldenbourg, R., Katoh, K. and Danuser, G. (2000). Mechanism of lateral movement of filopodia and radial actin bundles across neuronal growth cones. Biophys. J.78, 1176-1182.","DOI":"10.1016\/S0006-3495(00)76675-6"},{"key":"2021042517455044100_REF30","doi-asserted-by":"crossref","unstructured":"Pollard, T. D., Blanchoin, L. and Mullins, R. D. (2000). Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu. Rev. Biophys. Biomol. Struct.29, 545-576.","DOI":"10.1146\/annurev.biophys.29.1.545"},{"key":"2021042517455044100_REF31","doi-asserted-by":"crossref","unstructured":"Rottner, K., Behrendt, B., Small, J. V. and Wehland, J. (1999). VASP dynamics during lamellipodia protrusion. Nat. Cell Biol.1, 321-322.","DOI":"10.1038\/13040"},{"key":"2021042517455044100_REF32","doi-asserted-by":"crossref","unstructured":"Schaefer, A. W., Kabir, N. and Forscher, P. (2002). Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones. J. Cell Biol.158, 139-152.","DOI":"10.1083\/jcb.200203038"},{"key":"2021042517455044100_REF33","doi-asserted-by":"crossref","unstructured":"Small, J. V., Stradal, T., Vignal, E. and Rottner, K. (2002). The lamellipodium: where motility begins. Trends Cell Biol.12, 112-120.","DOI":"10.1016\/S0962-8924(01)02237-1"},{"key":"2021042517455044100_REF34","doi-asserted-by":"crossref","unstructured":"Snapper, S. B., Takeshima, F., Anton, I., Liu, C. H., Thomas, S. M., Nguyen, D., Dudley, D., Fraser, H., Purich, D., Lopez-Ilasaca, M. et al. (2001). N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nat. Cell Biol.3, 897-904.","DOI":"10.1038\/ncb1001-897"},{"key":"2021042517455044100_REF35","doi-asserted-by":"crossref","unstructured":"Steketee, M. and Tosney, K. W. (2001). Filopodial initiation and a novel filament-organizing center, the focal ring. Mol. Biol. Cell12, 2378-2395.","DOI":"10.1091\/mbc.12.8.2378"},{"key":"2021042517455044100_REF36","doi-asserted-by":"crossref","unstructured":"Steketee, M. B. and Tosney, K. W. (2002). Three functionally distinct adhesions in filopodia: shaft adhesions control lamellar extension. J. Neurosci.22, 8071-8083.","DOI":"10.1523\/JNEUROSCI.22-18-08071.2002"},{"key":"2021042517455044100_REF37","doi-asserted-by":"crossref","unstructured":"Suetsugu, S., Miki, H. and Takenawa, T. (1999). Identification of two human WAVE\/SCAR homologues as general actin regulatory molecules which associate with the Arp2\/3 complex. Biochem. Biophys. Res. Commun.260, 296-302.","DOI":"10.1006\/bbrc.1999.0894"},{"key":"2021042517455044100_REF38","doi-asserted-by":"crossref","unstructured":"Suetsugu, S., Miki, H. and Takenawa, T. (2002). Spatial and temporal regulation of actin polymerization for cytoskeleton formation through Arp2\/3 complex and WASP\/WAVE proteins. Cell Motil. Cytoskeleton51, 113-122.","DOI":"10.1002\/cm.10020"},{"key":"2021042517455044100_REF39","doi-asserted-by":"crossref","unstructured":"Takenawa, T. and Miki, H. (2001). WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci.114, 1801-1809.","DOI":"10.1242\/jcs.114.10.1801"},{"key":"2021042517455044100_REF40","doi-asserted-by":"crossref","unstructured":"Theriot, J. A. (2000). The polymerization motor. Traffic1, 19-28.","DOI":"10.1034\/j.1600-0854.2000.010104.x"},{"key":"2021042517455044100_","doi-asserted-by":"crossref","unstructured":"Theriot, J. A. and Mitchison, T. J. (1991). Actin microfilament dynamics in locomoting cells. Nature352, 126-131.","DOI":"10.1038\/352126a0"},{"key":"2021042517455044100_","doi-asserted-by":"crossref","unstructured":"Watanabe, N. and Mitchison, T. J. (2002). Single-molecule speckle analysis of actin filament turnover in lamellipodia. Science295, 1083-1086.","DOI":"10.1126\/science.1067470"},{"key":"2021042517455044100_REF43","doi-asserted-by":"crossref","unstructured":"Yeh, T. C., Ogawa, W., Danielsen, A. G. and Roth, R. A. (1996). Characterization and cloning of a 58\/53-kDa substrate of the insulin receptor tyrosine kinase. J. Biol. Chem.271, 2921-2928.","DOI":"10.1074\/jbc.271.6.2921"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/116\/2\/239\/1491548\/239.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/116\/2\/239\/1491548\/239.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T07:09:57Z","timestamp":1622531397000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/116\/2\/239\/27303\/Differential-localization-of-WAVE-isoforms-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,15]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,1,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.00233","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2003,1,15]]}}}