The RhoGEF DOCK10 is essential for dendritic spine morphogenesis

Mol Biol Cell. 2015 Jun 1;26(11):2112-27. doi: 10.1091/mbc.E14-08-1310. Epub 2015 Apr 7.


By regulating actin cytoskeleton dynamics, Rho GTPases and their activators RhoGEFs are implicated in various aspects of neuronal differentiation, including dendritogenesis and synaptogenesis. Purkinje cells (PCs) of the cerebellum, by developing spectacular dendrites covered with spines, represent an attractive model system in which to decipher the molecular signaling underlying these processes. To identify novel regulators of dendritic spine morphogenesis among members of the poorly characterized DOCK family of RhoGEFs, we performed gene expression profiling of fluorescence-activated cell sorting (FACS)-purified murine PCs at various stages of their postnatal differentiation. We found a strong increase in the expression of the Cdc42-specific GEF DOCK10. Depleting DOCK10 in organotypic cerebellar cultures resulted in dramatic dendritic spine defects in PCs. Accordingly, in mouse hippocampal neurons, depletion of DOCK10 or expression of a DOCK10 GEF-dead mutant led to a strong decrease in spine density and size. Conversely, overexpression of DOCK10 led to increased spine formation. We show that DOCK10 function in spinogenesis is mediated mainly by Cdc42 and its downstream effectors N-WASP and PAK3, although DOCK10 is also able to activate Rac1. Our global approach thus identifies an unprecedented function for DOCK10 as a novel regulator of dendritic spine morphogenesis via a Cdc42-mediated pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / growth & development*
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / physiology*
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis*
  • Neurons / metabolism
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Purkinje Cells / metabolism
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Signal Transduction
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism
  • cdc42 GTP-Binding Protein / metabolism
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / metabolism


  • Cdc42 protein, mouse
  • DOCK10 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Neuropeptides
  • Rac1 protein, mouse
  • Wasl protein, mouse
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Pak3 protein, mouse
  • p21-Activated Kinases
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein