First published online November 5, 2008
Journal of Cell Science 121, 2201e (2008)
© The Company of Biologists Limited
Axons are quick on the uptake
During development of the nervous system, axons are guided to their targets by neuronal growth cones, which are highly motile structures at the axonal distal tip. The growth cone is the major site of axonal endocytosis, but the pathways that govern growth-cone-membrane remodelling have remained elusive. Now, Flavia Valtorta and colleagues (p. 3757) identify a novel process of bulk endocytosis that occurs during axonal growth. Using cultured hippocampal neurons at 2-3 days in vitro, the authors observe bulk internalisation of the plasma-membrane marker FM4-64, and show that this correlates with growth-cone motility. The process shares several features with macropinocytosis – it occurs at sites of actin-based membrane ruffling, and requires the activity of PI3-kinase, the GTPase Rac1 and the pinocytic chaperone Pincher. Moreover, FM4-64 uptake is clathrin-independent and is distinct from synaptic-vesicle and endosomal recycling pathways. At later developmental stages (when synaptogenesis begins), bulk endocytosis is downregulated; concomitantly, depolarisation-dependent synaptic-vesicle recycling begins to occur. Thus, bulk endocytosis at the growth cone is developmentally regulated and might, the authors propose, account for the efficient remodelling of the growth-cone membrane during the early stages of neuronal development.

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Related articles in JCS:
- 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, and Flavia Valtorta
JCS 2008 121: 3757-3769.
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