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Neuron. 2016 Dec 7;92(5):1020-1035. doi: 10.1016/j.neuron.2016.10.014. Epub 2016 Nov 10.

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

Author information

1
National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bethesda, MD 20892, USA.
2
National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bethesda, MD 20892, USA. Electronic address: shengjs@gmail.com.
3
National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bethesda, MD 20892, USA. Electronic address: zhen0806@gmail.com.
4
Ecole Normale Supérieure, PSL Research University, CNRS, Inserm, Institut de Biologie de l'Ecole Normale Supérieure, F-75005 Paris, France.
5
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
6
National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Bethesda, MD 20892, USA. Electronic address: wul@ninds.nih.gov.

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.

PMID:
27840001
PMCID:
PMC5145734
DOI:
10.1016/j.neuron.2016.10.014
[Indexed for MEDLINE]
Free PMC Article

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