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Dominant role of lipid rafts L‐type calcium channel in activity‐dependent potentiation of large dense‐core vesicle exocytosis
Author(s) -
Park Yongsoo,
Kim KyongTai
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06148.x
Subject(s) - exocytosis , microbiology and biotechnology , protein kinase c , long term potentiation , marcks , biology , lipid raft , synaptic vesicle , vesicle , voltage dependent calcium channel , phosphorylation , chemistry , biochemistry , calcium , signal transduction , secretion , receptor , membrane , organic chemistry
Calcium influx triggers exocytosis by promoting vesicle fusion with the plasma membrane. However, different subtypes of voltage‐gated calcium channel (VGCC) have distinct roles in exocytosis. We previously reported that repetitive stimulation induces activity‐dependent potentiation (ADP) which represents the increase of neurotransmitter release. Here, we show that L‐type VGCC have a dominant role in ADP of large dense‐core vesicle (LDCV) exocytosis. Repetitive stimulation activating VGCC can induce ADP, whereas activation of bradykinin (BK) G protein‐coupled receptors or purinergic P2X cation channels can not. L‐type VGCC has the dominant role in ADP of LDCV exocytosis by regulating Protein Kinase C (PKC)‐epsilon translocation and phosphorylation of myristoylated alanine‐rich C kinase substrate (MARCKS), a target molecule of PKC‐epsilon. We provide evidence that L‐type VGCC, PKC‐epsilon, and MARCKS, but not Q‐type VGCC, are selectively located in lipid rafts. Also, PKC‐epsilon translocation induced by L‐type VGCC activation occurs in lipid rafts. Disruption of lipid rafts abolishes ADP of LDCV exocytosis and changes the fusion pore kinetics without affecting the first stimulation‐induced exocytosis, showing that lipid rafts are involved in the potentiation process. Taken together, we suggest that L‐type VGCC in lipid rafts selectively mediates ADP of LDCV exocytosis by regulating PKC‐epsilon translocation and MARCKS phosphorylation.