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

Dario Bonanomi, Eugenio F. Fornasiero, Gregorio Valdez, Simon Halegoua, Fabio Benfenati, Andrea Menegon, Flavia Valtorta

Research output: Contribution to journalArticlepeer-review


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 exoendocytosis. 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.

Original languageEnglish
Pages (from-to)3757-3769
Number of pages13
JournalJournal of Cell Science
Issue number22
Publication statusPublished - Nov 15 2008


  • Axolemma
  • Endocytosis
  • Fluorescence microscopy
  • Synaptic vesicle
  • Trafficking

ASJC Scopus subject areas

  • Cell Biology


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