Abstract：
: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.
journal_name
Neuronjournal_title
Neuronauthors
Nicholson-Fish JC,Kokotos AC,Gillingwater TH,Smillie KJ,Cousin MAdoi
10.1016/j.neuron.2015.10.043subject
Has Abstractpub_date
2015-12-02 00:00:00pages
973-984issue
5eissn
0896-6273issn
1097-4199pii
S0896-6273(15)00937-Xjournal_volume
88pub_type
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