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Dock4 regulates dendritic development in hippocampal neurons

✍ Scribed by Shuhei Ueda; Satoshi Fujimoto; Kiyo Hiramoto; Manabu Negishi; Hironori Katoh

Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
445 KB
Volume
86
Category
Article
ISSN
0360-4012

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✦ Synopsis

Abstract

Dendrite development is required for establishing proper neuronal connectivity. Rho‐family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up‐regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C‐terminal Crk‐binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley‐Liss, Inc.

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