Journal
JOURNAL OF BIOMEDICAL RESEARCH
Volume 35, Issue 5, Pages 339-350Publisher
NANJING MEDICAL UNIV
DOI: 10.7555/JBR.34.20200095
Keywords
retrograde trafficking; vesicular targeting; synaptic vesicle-like vesicles; synaptic vesicles; PC12
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Funding
- National Natural Science Foundation of China [31371436, 8157051134]
- Nanjing Medical University
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SNX5 is identified as a novel regulator for both stability and SV targeting of VAChT.
Accurate targeting of vesicular acetylcholine transporter (VAChT) to synaptic vesicles (SVs) is indispensable for efficient cholinergic transmission. Previous studies have suggested that the dileucine motif within the C-terminus of the transporter is sufficient for its targeting to SVs. However, the cytosolic machinery underlying specific regulation of VAChT trafficking and targeting to SVs is still unclear. Here we used the C-terminus of VAChT as a bait in a yeast two-hybrid screen to identify sorting nexin 5 (SNX5) as its novel interacting protein. SNX5 was detected in the SVs enriched LP2 subcellular fraction of rat brain homogenate and showed strong colocalization with VAChT in both brain sections and PC12 cells. Binding assays suggested that the C-terminal domain of VAChT can interact with both BAR and PX domain of SNX5. Depletion of SNX5 enhanced the degradation of VAChT and the process was mediated through the lysosomal pathway. More importantly, we found that, in PC12 cells, the depletion of SNX5 expression significantly decreased the synaptic vesicle-like vesicles (SVLVs) localization of VAChT. Therefore, the results suggest that SNX5 is a novel regulator for both stability and SV targeting of VAChT.
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