Identification of a developmentally regulated pathway of membrane retrieval in neuronal growth cones

J Cell Sci. 2008 Nov 15;121(Pt 22):3757-69. doi: 10.1242/jcs.033803. Epub 2008 Oct 21.

Abstract

The growth-cone plasma membrane constantly reconfigures during axon navigation and upon target recognition. The identity and regulation of the membrane pathway(s) participating in remodeling of the growth-cone surface remain elusive. Here, we identify a constitutive, high-capacity plasma-membrane-recycling activity in the axonal growth cones, which is mediated by a novel bulk endocytic pathway that is mechanistically related to macropinocytosis. This pathway generates large compartments at sites of intense actin-based membrane ruffling through the actions of phosphatidylinositol 3-kinase, the small GTPase Rac1 and the pinocytic chaperone Pincher. At early developmental stages, bulk endocytosis is the primary endocytic pathway for rapid retrieval of the growth-cone plasma membrane. At later stages, during the onset of synaptogenesis, an intrinsic program of maturation leads to downregulation of basal bulk endocytosis and the emergence of depolarization-induced synaptic-vesicle exo-endocytosis. We propose that the control of bulk membrane retrieval contributes to the homeostatic regulation of the axonal plasma membrane and to growth-cone remodeling during axonal outgrowth. In addition, we suggest that the downregulation of bulk endocytosis during synaptogenesis might contribute to the preservation of synaptic-vesicle specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Endocytosis
  • Growth Cones / metabolism*
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis
  • Neurons / cytology*
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Synaptic Vesicles / metabolism