Rac1-mediated endocytosis during Ephrin-A2- and semaphorin 3A-induced growth cone collapse

William M. Jurney, Gianluca Gallo, Paul C. Letourneau, Steven C. McLoon

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Negative guidance molecules are important for guiding the growth of axons and ultimately for determining the wiring pattern in the developing nervous system. In tissue culture, growth cones at the tips of growing axons collapse in response to negative guidance molecules, such as ephrin-A2 and semaphorin 3A. The small GTPase Rac1 is involved in growth cone collapse, but the nature of its role is not clear. Rac1 activity assays showed that Rac1 is transiently inactivated after treatment with ephrin-A2. Ephrin-induced growth cone collapse, however, correlated with resumption of Rac1 activity. We demonstrate that Rac1 is required for endocytosis of the growth cone plasma membrane and reorganization of F-actin but not for the depolymerization of F-actin during growth cone collapse in response to ephrin-A2 and semaphorin 3A. Rac1, however, does not regulate constitutive endocytosis in growth cones. These findings show that in response to negative guidance molecules, the function of Rac1 changes from promoting actin polymerization associated with axon growth to driving endocytosis of the plasma membrane, resulting in growth cone collapse. Furthermore, Rac1 antisense injected into the embryonic chick eye in vivo caused the retinotectal projection to develop without normal topography in a manner consistent with Rac1 having an obligatory role in mediating ephrin signaling.

Original languageEnglish (US)
Pages (from-to)6019-6028
Number of pages10
JournalJournal of Neuroscience
Volume22
Issue number14
DOIs
StatePublished - Jul 15 2002

Keywords

  • Actin
  • Axon guidance
  • Development
  • Endocytosis
  • Ephrin
  • Growth cone
  • Retina
  • Semaphorin

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