Regulatory role of sorting nexin 5 in protein stability and vesicular targeting of vesicular acetylcholine transporter to synaptic vesicle-like vesicles in PC12 cells
Meihen Sun1
Xu Han1
Fei Chang2
Hongfei Xu3
Lesley Colgan4
Yongjian Liu1
1.Jiangsu Key Laboratory of Xenotransplantation,and Department of Medical Genetics,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Neuroscience Program,University of Utah School of Medicine,Salt Lake City,UT 84112,USA3.Department of Neurology,University of California San Francisco School of Medicine,San Francisco,CA 94143,USA4.Max Planck Florida Institute for Neuroscience,Jupiter,FL 33458,USA
摘要：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 PC 12 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 PC 12 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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分类号：Q7(分子生物学)
论文发表日期：2021-09-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 339-350 )
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