Cerebral cortex (New York, N.Y. 1991), 2015-09, Vol.25 (9), p.2863-2875
2015
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Details
- Autor(en) / Beteiligte
- Titel
- ADF/Cofilin Controls Synaptic Actin Dynamics and Regulates Synaptic Vesicle Mobilization and Exocytosis
- Ist Teil von
- Cerebral cortex (New York, N.Y. 1991), 2015-09, Vol.25 (9), p.2863-2875
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2015
- Quelle
- Oxford Journals 2020 Medicine
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1047-3211eISSN: 1460-2199DOI: 10.1093/cercor/bhu081Titel-ID: cdi_proquest_miscellaneous_1704347478
- Format
- –
- Schlagworte
- Actins - metabolism, Animals, Cofilin 1 - genetics, Cofilin 1 - metabolism, Destrin - genetics, Destrin - metabolism, Electric Stimulation, Excitatory Postsynaptic Potentials - genetics, Excitatory Postsynaptic Potentials - physiology, Exocytosis - drug effects, Exocytosis - genetics, Exocytosis - physiology, Glutamic Acid - metabolism, Green Fluorescent Proteins - genetics, Green Fluorescent Proteins - metabolism, Mice, Mice, Transgenic, Mutation - genetics, Neurons - drug effects, Neurons - physiology, Neurons - ultrastructure, Phosphorylation, Potassium Chloride - pharmacology, Prosencephalon - cytology, Protein Transport - genetics, Protein Transport - physiology, SNARE Proteins - metabolism, Synapses - drug effects, Synapses - physiology, Synapses - ultrastructure, Synaptic Vesicles - metabolism