Overexpression of complexin in PC12 cells inhibits exocytosis by preventing SNARE complex recycling.
Complexin is an important protein that functions during Ca2+-dependent neurotransmitter release. Substantial evidence supports that complexin performs its role through rapid interaction with SNARE complex with high affinity. However, alpha-SNAP/NSF, which can disassemble the cis-SNARE complex in the presence of MgATP, competes with complexin to bind to SNARE complex. In addition, injection of alpha-SNAP into chromaffin cells enhances the size of the readily releasable pool, and mutation disrupting the ATPase activity of NSF results in the accumulation of SNARE complex. Thus, whether high concentrations of complexin could result in a reverse result is unclear. In this paper, we demonstrate that when stably overexpressed in PC12 cells, high levels of complexin result in the accumulation of SNARE complex. This in turn leads to a reduction in the size of the readily releasable pool of large dense core vesicles. These results suggest that high levels of complexin seem to prevent SNARE complex recycling, presumably by displacing NSF and alpha-SNAP from SNARE complex.
Liu
Jingguo
J
Department of Biological Sciences and Biotechnology, State-Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Guo
Ting
T
Wu
Ju
J
Bai
Xiaochen
X
Zhou
Qiang
Q
Sui
Sen-Fang
SF
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D016716:PC12 Cells; D051381:Rats; D050600:SNARE Proteins / Q000502:physiology*; D022142:Secretory Vesicles / Q000502:physiology
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; C095993:complexin II; D004298:Dopamine