Journal Article

ADF/Cofilin Controls Synaptic Actin Dynamics and Regulates Synaptic Vesicle Mobilization and Exocytosis

Michael Wolf, Anika-Maria Zimmermann, Andreas Görlich, Christine B. Gurniak, Marco Sassoè-Pognetto, Eckhard Friauf, Walter Witke and Marco B. Rust

in Cerebral Cortex

Volume 25, issue 9, pages 2863-2875
Published in print September 2015 | ISSN: 1047-3211
Published online April 2014 | e-ISSN: 1460-2199 | DOI: https://dx.doi.org/10.1093/cercor/bhu081
ADF/Cofilin Controls Synaptic Actin Dynamics and Regulates Synaptic Vesicle Mobilization and Exocytosis

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  • Clinical Neuroscience
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Actin is a regulator of synaptic vesicle mobilization and exocytosis, but little is known about the mechanisms that regulate actin at presynaptic terminals. Genetic data on LIMK1, a negative regulator of actin-depolymerizing proteins of the ADF/cofilin family, suggest a role for ADF/cofilin in presynaptic function. However, synapse physiology is fully preserved upon genetic ablation of ADF in mice, and n-cofilin mutant mice display defects in postsynaptic plasticity, but not in presynaptic function. One explanation for this phenomenon is overlapping functions of ADF and n-cofilin in presynaptic physiology. Here, we tested this hypothesis and genetically removed ADF together with n-cofilin from synapses. In double mutants for ADF and n-cofilin, synaptic actin dynamics was impaired and more severely affected than in single mutants. The resulting cytoskeletal defects heavily affected the organization, mobilization, and exocytosis of synaptic vesicles in hippocampal CA3–CA1 synapses. Our data for the first time identify overlapping functions for ADF and n-cofilin in presynaptic physiology and vesicle trafficking. We conclude that n-cofilin is a limiting factor in postsynaptic plasticity, a function which cannot be substituted by ADF. On the presynaptic side, the presence of either ADF or n-cofilin is sufficient to control actin remodeling during vesicle release.

Keywords: CA3–CA1 synapse; hippocampus; neurotransmitter release; presynaptic physiology; synaptic plasticity

Journal Article.  8455 words.  Illustrated.

Subjects: Neurology ; Clinical Neuroscience ; Neuroscience

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