Actin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses

Xin Sheng Wu, Sung Hoon Lee, Jiansong Sheng, Zhen Zhang, Wei Dong Zhao, Dongsheng Wang, Yinghui Jin, Patrick Charnay, James M. Ervasti, Ling Gang Wu

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Abstract

Mechanical force is needed to mediate endocytosis. Whether actin, the most abundant force-generating molecule, is essential for endocytosis is highly controversial in mammalian cells, particularly synapses, likely due to the use of actin blockers, the efficiency and specificity of which are often unclear in the studied cell. Here we addressed this issue using a knockout approach combined with measurements of membrane capacitance and fission pore conductance, imaging of vesicular protein endocytosis, and electron microscopy. We found that two actin isoforms, β- and γ-actin, are crucial for slow, rapid, bulk, and overshoot endocytosis at large calyx-type synapses, and for slow endocytosis and bulk endocytosis at small hippocampal synapses. Polymerized actin provides mechanical force to form endocytic pits. Actin also facilitates replenishment of the readily releasable vesicle pool, likely via endocytic clearance of active zones. We conclude that polymerized actin provides mechanical force essential for all kinetically distinguishable forms of endocytosis at synapses.

Original languageEnglish (US)
Pages (from-to)1020-1035
Number of pages16
JournalNeuron
Volume92
Issue number5
DOIs
StatePublished - Dec 7 2016

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Wu, X. S., Lee, S. H., Sheng, J., Zhang, Z., Zhao, W. D., Wang, D., Jin, Y., Charnay, P., Ervasti, J. M., & Wu, L. G. (2016). Actin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses. Neuron, 92(5), 1020-1035. https://doi.org/10.1016/j.neuron.2016.10.014