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However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)\u2013mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac.<\/jats:p>","DOI":"10.1091\/mbc.e12-11-0782","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T22:59:32Z","timestamp":1364425172000},"page":"1602-1613","source":"Crossref","is-referenced-by-count":45,"title":["Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation"],"prefix":"10.1091","volume":"24","author":[{"given":"Shuhei","family":"Ueda","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Negishi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, 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