Blog
About

16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Rac GEF Dock4, recently reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia, is highly concentrated in dendritic spines in hippocampal neurons and is implicated in spine formation through interaction with the actin-binding protein cortactin.

          Abstract

          In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. 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)–mediated 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.

          Related collections

          Author and article information

          Contributors
          Role: Monitoring Editor
          Journal
          Mol Biol Cell
          Mol. Biol. Cell
          molbiolcell
          mbc
          Mol. Bio. Cell
          Molecular Biology of the Cell
          The American Society for Cell Biology
          1059-1524
          1939-4586
          15 May 2013
          : 24
          : 10
          : 1602-1613
          Affiliations
          Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
          Yale University
          Author notes
          1Address correspondence to: Hironori Katoh ( hirokato@ 123456pharm.kyoto-u.ac.jp ).
          Article
          E12-11-0782
          10.1091/mbc.E12-11-0782
          3655820
          23536706
          © 2013 Ueda et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0).

          “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.

          Product
          Categories
          Articles
          Signaling

          Molecular biology

          Comments

          Comment on this article