title: Physical and functional interaction of Snapin with Cav1.3 calcium channel impacts channel protein trafficking in atrial myocytes.
abstract: The L-type Ca2+channel (LTCC) Cav1.3 plays a critical role in generating electrical activity in atrial myocytes and cardiac pacemaker cells. However, the molecular and functional basis of Cav1.3 modulation in atrial myocytes has not yet been fully understood. By using the yeast two-hybrid system (Y2H), a Cav1.3-associated protein was screened, which was identified as Snapin. Physical interaction and co-localization between Snapin and Cav1.3 were then confirmed in both the heterologous expression system and mouse atrial myocytes. Direct interaction between them was additionally addressed in a GST pull down assay. Furthermore, both total and membrane expressions of Cav1.3 were significantly impaired by Snapin overexpression, resulting in the ubiquitin-proteasomal degradation of Cav1.3 and a consequent reduction of the densities of whole-cell ICa-L. Snapin-induced down-regulation of Cav1.3 was reversed by SNAP-23 competitively. What is more important is that the depressed-expression of Cav1.3 paralleled with enhanced-expression of Snapin was documented in atrial samples from atrial fibrillation (AF) patients. Our results provide the evidence of a direct regulatory role of Snapin on Cav1.3 channels in atrial myocytes, and highlight a potential role of Snapin in the regulation of Cav1.3 in atrial arrhythmogenesis.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Sun
authors.affiliation: Anesthesia Department of The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, China.
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China; Department of Nephrology at the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China. Electronic address: zhangzhao@njnu.edu.cn.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006325:Heart Atria / Q000166:cytology*; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D050766:Qb-SNARE Proteins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C472073:CACNA1D protein, human; C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D050766:Qb-SNARE Proteins; C118519:SNAPIN protein, human; C498451:Snapin protein, mouse; D033921:Vesicular Transport Proteins
keywords: Atrial fibrillation; Cav1.3; Membrane trafficking; SNARE; Snapin