Synaptotagmin VII (Syt VII), which has a higher Ca2+ affinity and slower disassembly kinetics with lipid than Syt I and Syt IX, was regarded as being uninvolved in synaptic vesicle (SV) exocytosis but instead possibly as a calcium sensor for the slower kinetic phase of dense core vesicles (DCVs) release. By using high temporal resolution capacitance and amperometry measurements, it was demonstrated that the knockdown of endogenous Syt VII attenuated the fusion of DCV with the plasma membrane, reduced the amplitude of the exocytotic burst of the Ca2+-triggered DCV release without affecting the slope of the sustained component, and blocked the fusion pore expansion. This suggests that Syt VII is the Ca2+ sensor of DCV fusion machinery and is an essential factor for the establishment and maintenance of the pool size of releasable DCVs in PC12 cells.
LI JiangLi1, XIAO Yang1, ZHOU Wei1, WU ZhengXing1, ZHANG RongYing1· & XU Tao1,2· 1 Key Laboratory of Molecular Biophysics of the Ministry of Education, Institute of Biophysics and Biochemistry, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Animals integrate various environmental stimuli within the nervous system to generate proper behavioral responses.However,the underlying neural circuits and molecular mechanisms are largely unknown.The insulinlike signaling pathway is known to regulate dauer formation,fat metabolism,and longevity in Caenorhabditis elegans(C.elegans).Here,we show that this highly conserved signaling pathway also functions in the integrative response to an olfactory diacetyl and a gustatory Cu^(2+) stimuli.Worms of wild-type N2 Bristol displayed a strong avoidance to the Cu^(2+) barrier in the migration pathway to the attractive diacetyl.Mutants of daf-2(insulin receptor),daf-18(PTEN lipid phosphatase),pdk-1(phosphoinositide-dependent kinase),akt-1/-2(Akt/PKB kinase)and sgk-1(serum-and glucocorticoidinducible kinase)show severe defects in the elusion from the Cu^(2+) .Mutations in DAF-16,a forkhead-type transcriptional factor,suppress the integrative defects of daf-2 and akt-1/-2 mutants.We further report that neither cGMP nor TGFβpathways,two other dauer formation regulators,likely plays a role in the integrative learning.These results suggest that the insulin-like signaling pathway constitutes an essential component for sensory integration and decision-making behavior plasticity.
