First Author | Nicholson-Fish JC | Year | 2015 |
Journal | Neuron | Volume | 88 |
Issue | 5 | Pages | 973-984 |
PubMed ID | 26607000 | Mgi Jnum | J:228735 |
Mgi Id | MGI:5708774 | Doi | 10.1016/j.neuron.2015.10.043 |
Citation | Nicholson-Fish JC, et al. (2015) VAMP4 Is an Essential Cargo Molecule for Activity-Dependent Bulk Endocytosis. Neuron 88(5):973-84 |
abstractText | 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. |