Neurons contact each other mostly by synaptic transmission at synapses. Synaptic transmission is mediated by calcium-triggered vesicle fusion with the plasma membrane, which releases transmitter molecules that act on postsynaptic transmitter receptors. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle exocytosis, which are the building block for synaptic transmission and thus the signaling process in the neuronal network. My progress in the last year is listed in the following. First, the widely observed rapid endocytosis is generally assumed to recycle vesicles within the readily releasable pool (RRP) via a kiss-and-run mechanism that involves rapid opening and closure of a fusion pore at the release site. Here we found that rapid endocytosis do not recycle vesicles to the RRP, but to a large recycling pool (Wu &Wu, J Neurosci, 2009). This finding challenges the current model that the function of the rapid kiss-and-run fusion is to recycle vesicles rapidly within the RRP for rapid reuse. Second, we found calcium/calmodulin activates a phosphotase calcineurin, which in turn regulates vesicle cycling by which synaptic transmission is maintained during repetitive stimulation (Sun et al., J Neurosci, 2010).

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2010
Total Cost
$1,326,078
Indirect Cost
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State
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Yuan, Jie; Zhang, Fan; Hallahan, Dennis et al. (2018) Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors. J Exp Clin Cancer Res 37:181
Shin, Wonchul; Ge, Lihao; Arpino, Gianvito et al. (2018) Visualization of Membrane Pore in Live Cells Reveals a Dynamic-Pore Theory Governing Fusion and Endocytosis. Cell 173:934-945.e12
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Wu, Xin-Sheng; Lee, Sung Hoon; Sheng, Jiansong et al. (2016) Actin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses. Neuron 92:1020-1035
Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul et al. (2016) Hemi-fused structure mediates and controls fusion and fission in live cells. Nature 534:548-52
Baydyuk, Maryna; Xu, Jianhua; Wu, Ling-Gang (2016) The calyx of Held in the auditory system: Structure, function, and development. Hear Res 338:22-31
Park, Soonhong; Ahuja, Malini; Kim, Min Seuk et al. (2016) Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV. EMBO Rep 17:266-78
Baydyuk, Maryna; Wu, Xin-Sheng; He, Liming et al. (2015) Brain-derived neurotrophic factor inhibits calcium channel activation, exocytosis, and endocytosis at a central nerve terminal. J Neurosci 35:4676-82
Wu, Ling-Gang; Hamid, Edaeni; Shin, Wonchul et al. (2014) Exocytosis and endocytosis: modes, functions, and coupling mechanisms. Annu Rev Physiol 76:301-31
Chiang, Hsueh-Cheng; Shin, Wonchul; Zhao, Wei-Dong et al. (2014) Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles. Nat Commun 5:3356

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