Rab3A is a new interacting partner of synaptotagmin I and may modulate synaptic membrane fusion through a competitive mechanism.
Rab3 and synaptotagmin have been reported to be the key proteins that have opposite actions but cooperatively play critical regulatory roles in selecting and limiting the number of vesicles released at central synapses. However, the exact mechanism has not been fully understood. In this study, Rab3A and synaptotagmin I, the most abundant isoforms of Rab3 and synaptotagmin, respectively, in brain were for the first time demonstrated to directly interact with each other in a Ca(2+)-independent manner, and the KKKK motif in the C2B domain of synaptotagmin I was a key site for the Rab3A binding, which was further confirmed by the competitive inhibition of inositol hexakisphosphate. Further studies demonstrated that Rab3A competitively affected the synaptotagmin I interaction with syntaxin 1B that was involved in membrane fusion during the synaptic vesicle exocytosis. These data indicate that Rab3A is a new synaptotagmin I interacting partner and may participate in the regulation of synaptic membrane fusion and thus the vesicle exocytosis by competitively modulating the interaction of synaptotagmin with syntaxin of the t-SNARE complex in presynaptic membranes.
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China; Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, PR China.
Chunliang
C
Xie
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Jianglin
J
Li
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Tianyao
T
Guo
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Yizhong
Y
Yan
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Cheng
C
Tang
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Ying
Y
Wang
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
Ping
P
Chen
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China. Electronic address: wang_xianchun@263.net.
Xianchun
X
Wang
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China. Electronic address: liangsp@hunnu.edu.cn.
Songping
S
Liang
D020816:Amino Acid Motifs; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis; D008561:Membrane Fusion; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000378:metabolism*; D050863:Synaptotagmin I / Q000737:chemistry / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism*
D050863:Synaptotagmin I; D050827:Syntaxin 1; D020826:rab3A GTP-Binding Protein; D002118:Calcium
Interaction; Mechanism; Membrane fusion; Rab3A; Synapse; Synaptotagmin I