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VAMP4 Is an Essential Cargo Molecule for Activity-Dependent Bulk Endocytosis.

Authors: Nicholson-Fish, JC  Kokotos, AC  Gillingwater, TH  Smillie, KJ  Cousin, MA 
Citation: Nicholson-Fish JC, etal., Neuron. 2015 Dec 2;88(5):973-84. doi: 10.1016/j.neuron.2015.10.043. Epub 2015 Nov 19.
Pubmed: (View Article at PubMed) PMID:26607000
DOI: Full-text: DOI:10.1016/j.neuron.2015.10.043

The accurate formation of synaptic vesicles (SVs) and incorporation of their protein cargo during endocytosis is critical for the maintenance of neurotransmission. During intense neuronal activity, a transient and acute accumulation of SV cargo occurs at the plasma membrane. Activity-dependent bulk endocytosis (ADBE) is the dominant SV endocytosis mode under these conditions; however, it is currently unknown how ADBE mediates cargo retrieval. We examined the retrieval of different SV cargo molecules during intense stimulation using a series of genetically encoded pH-sensitive reporters in neuronal cultures. The retrieval of only one reporter, VAMP4-pHluorin, was perturbed by inhibiting ADBE. This selective recovery was confirmed by the enrichment of endogenous VAMP4 in purified bulk endosomes formed by ADBE. VAMP4 was also essential for ADBE, with a cytoplasmic di-leucine motif being critical for this role. Therefore, VAMP4 is the first identified ADBE cargo and is essential for this endocytosis mode to proceed.

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CRRD Object Information
CRRD ID: 11058152
Created: 2016-04-13
Species: All species
Last Modified: 2016-04-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.