PKC-induced sensitization of Ca2+-dependent exocytosis is mediated by reducing the Ca2+ cooperativity in pituitary gonadotropes.
The highly cooperative nature of Ca2+-dependent exocytosis is very important for the precise regulation of transmitter release. It is not known whether the number of binding sites on the Ca2+ sensor can be modulated or not. We have previously reported that protein kinase C (PKC) activation sensitizes the Ca2+ sensor for exocytosis in pituitary gonadotropes. To further unravel the underlying mechanism of how the Ca2+ sensor is modulated by protein phosphorylation, we have performed kinetic modeling of the exocytotic burst and investigated how the kinetic parameters of Ca2+-triggered fusion are affected by PKC activation. We propose that PKC sensitizes exocytosis by reducing the number of calcium binding sites on the Ca2+ sensor (from three to two) without significantly altering the Ca2+-binding kinetics. The reduction in the number of Ca2+-binding steps lowers the threshold for release and up-regulates release of fusion-competent vesicles distant from Ca2+ channels.
Yang
Hua
H
Institute of Biophysics and Biochemistry, School of Life Science and Technology, Huazhong Univeristy of Science and Technology, Wuhan, P.R. China.
Liu
Huisheng
H
Hu
Zhitao
Z
Zhu
Hongliang
H
Xu
Tao
T
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects*; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011493:Protein Kinase C / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000378:metabolism
D006065:Gonadotropins, Pituitary; D044169:Receptors, Calcium-Sensing; D011493:Protein Kinase C; D002118:Calcium