Visualization of Membrane Pore in Live Cells Reveals a Dynamic-Pore Theory Governing Fusion and Endocytosis

Wonchul Shin, Lihao Ge, Gianvito Arpino, Seth A. Villarreal, Edaeni Hamid, Huisheng Liu, Wei Dong Zhao, Peter J. Wen, Hsueh Cheng Chiang, Ling Gang Wu

研究成果: Article同行評審

76 引文 斯高帕斯(Scopus)

摘要

Fusion is thought to open a pore to release vesicular cargoes vital for many biological processes, including exocytosis, intracellular trafficking, fertilization, and viral entry. However, fusion pores have not been observed and thus proved in live cells. Its regulatory mechanisms and functions remain poorly understood. With super-resolution STED microscopy, we observed dynamic fusion pore behaviors in live (neuroendocrine) cells, including opening, expansion, constriction, and closure, where pore size may vary between 0 and 490 nm within 26 milliseconds to seconds (vesicle size: 180–720 nm). These pore dynamics crucially determine the efficiency of vesicular cargo release and vesicle retrieval. They are generated by competition between pore expansion and constriction. Pharmacology and mutation experiments suggest that expansion and constriction are mediated by F-actin-dependent membrane tension and calcium/dynamin, respectively. These findings provide the missing live-cell evidence, proving the fusion-pore hypothesis, and establish a live-cell dynamic-pore theory accounting for fusion, fission, and their regulation. The missing live-cell evidence proving the fusion pore hypothesis reveals metastable pores that are two orders of magnitude larger than previously thought and can constrict and close instantly or slowly.

原文English
頁(從 - 到)934-945.e12
期刊Cell
173
發行號4
DOIs
出版狀態Published - 2018 五月 3

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)

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