Open AccessSoluble α-synuclein facilitates priming and fusion by releasing Ca2+ from thapsigargin-sensitive Ca2+ pool in PC12 cells
Author(s) -
Chien Chang Huang,
Tai-Yu Chiu,
Tzu Ying Lee,
Hsin Jui Hsieh,
Chung Chih Lin,
LungSen Kao
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.213017
Subject(s) - exocytosis , thapsigargin , microbiology and biotechnology , vesicle fusion , biology , vesicle , munc 18 , lipid bilayer fusion , kiss and run fusion , priming (agriculture) , population , fluorescence recovery after photobleaching , biophysics , synaptic vesicle , biochemistry , secretion , endoplasmic reticulum , membrane , botany , germination , demography , sociology
α-Synuclein is associated with Parkinson's disease. α-Synuclein is mainly localized in presynaptic terminals and regulates exocytosis, but its physiological roles remain controversial. We studied effects of soluble and aggregated α-synuclein on exocytosis and explored the molecular mechanism by which α-synuclein interacts with regulatory proteins, including Rab3A, Munc13-1 and Munc18-1, in order to regulate exocytosis. Using fluorescence recovery after photobleaching, overexpressed α-synuclein in PC12 cells was found to be in a monomeric form, which promotes exocytosis. In contrast, aggregated α-synuclein induced by lactacystin inhibits exocytosis. Our results show that α-synuclein is involved in vesicle priming and fusion. α-Synuclein and PMA, which is known to enhance vesicle priming mediated by Rab3A, Munc13-1 and Munc18-1, act on the same population of vesicles, but regulate priming independently. Furthermore, the results show a novel effects of α-synuclein on mobilizing Ca2+ release from thapsigargin-sensitive calcium pools to enhance the ATP-induced [Ca2+]i increase, which enhances vesicle fusion. Our results provide a detailed understanding of the action of α-synuclein during the final steps of exocytosis.