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FARP2 triggers signals for Sema3A-mediated axonal repulsion

Toyofuku, Toshihiko, Yoshida, Junko, Sugimoto, Tamiko, Zhang, Hong, Kumanogoh, Atsushi, Hori, Masatsugu, Kikutani, Hitoshi·2005·Nature Neuroscience
DOI 10.1038/nn1596
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Abstract

Sema3A, a prototypical semaphorin, acts as a chemorepellent or a chemoattractant for axons by activating a receptor complex comprising neuropilin-1 as the ligand-binding subunit and plexin-A1 as the signal-transducing subunit. How the signals downstream of plexin-A1 are triggered upon Sema3A stimulation, however, is unknown. Here we show that, in the presence of neuropilin-1, the FERM domain-containing guanine nucleotide exchange factor (GEF) FARP2 associates directly with plexin-A1. Sema3A binding to neuropilin-1 induces the dissociation of FARP2 from plexin-A1, resulting in activation of FARP2's Rac GEF activity, Rnd1 recruitment to plexin-A1, and downregulation of R-Ras. Simultaneously, the FERM domain of FARP2 sequesters phosphatidylinositol phosphate kinase type I isoform PIPKIgamma661 from talin, thereby inhibiting its kinase activity. These activities are required for Sema3A-mediated repulsion of outgrowing axons and suppression of neuronal adhesion. We therefore conclude that FARP2 is a key molecule involved in the response of neuronal growth cones to class-3 semaphorins.

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Cited by

Metadata

Authors
Toyofuku, T., Yoshida, J., Sugimoto, T., Zhang, H., Kumanogoh, A., Hori, M., & Kikutani, H.
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2005-11-13
Volume
8
Issue
12
Pages
1712-1719
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/nn1596
Cited by
191
References
2
Language
en
Licence
www.springer.com/tdm (unspecified)

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