PKC-induced sensitization of Ca2+-dependent exocytosis is mediated by reducing the Ca2+ cooperativity in pituitary gonadotropes |
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| Authors: | Yang Hua Liu Huisheng Hu Zhitao Zhu Hongliang Xu Tao |
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| Affiliation: | Institute of Biophysics and Biochemistry, School of Life Science and Technology, Huazhong Univeristy of Science and Technology, Wuhan, P.R. China. |
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| Abstract: | 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. |
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| Keywords: | exocytosis kinetic modeling Ca2+ dependency fusion protein phosphorylation |
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