Journal
JOURNAL OF CELL BIOLOGY
Volume 162, Issue 1, Pages 113-124Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200301006
Keywords
ARF; clathrin coat assembly; PIPKI gamma; PIP2 formation; endocytosis
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Funding
- NIDDK NIH HHS [DK 54913] Funding Source: Medline
- NINDS NIH HHS [R37 NS036251, R01 NS036251, NS 36251] Funding Source: Medline
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Clathrin-mediated endocytosis of synaptic vesicle membranes involves the recruitment of clathrin and AP-2 adaptor complexes to the presynaptic plasma membrane. Phosphoinositides have been implicated in nucleating coat assembly by directly binding to several endocytotic proteins including AP-2 and AP180. Here, we show that the stimulatory effect of ATP and GTPgammaS on clathrin coat recruitment is mediated at least in part by increased levels Of PIP2. We also provide evidence for a role of ADP-ribosylation factor 6 (ARF6) via direct stimulation of a synaptically enriched phosphatidylinositol 4-phosphate 5-kinase type Igamma (PIPKIgamma), in this effect. These data suggest a model according to which activation of PIPKIgamma by ARF6-GTP facilitates clathrin-coated pit assembly at the synapse.
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