Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons.
Cofilin, the major actin depolymerizing factor, modulates actin dynamics that contribute to spine morphology, synaptic transmission and plasticity. Much evidence implicates the cofilin inactivation kinase LIMK in synaptic function, but little is known about the cofilin activation phosphatase Slingshot in this regard. In this study, we found that suppressing endogenous Slingshot with small RNA interference or function-blocking antibody led to a dramatic reduction of AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) in cortical neurons. Perturbation of Slingshot function also diminished the ability to express synaptic plasticity. Inactivating cofilin or disturbing actin dynamics reduced AMPAR-EPSCs in a Slingshot-dependent manner. Moreover, surface GluR 1 and synaptic GluR2/3 clusters were reduced by Slingshot knockdown. Our data suggest that Slingshot plays a pivotal role in AMPAR trafficking and synaptic transmission by controlling actin cytoskeleton via cofilin activation.
Yuen
Eunice Y
EY
Department of Physiology and Biophysics and New York State Center of Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY 14214, USA.
Liu
Wenhua
W
Kafri
Tal
T
van Praag
Henriette
H
Yan
Zhen
Z
D000199:Actins / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D051338:Cofilin 1 / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics / Q000502:physiology; D008840:Microfilament Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D051381:Rats; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D000199:Actins; D051338:Cofilin 1; D008840:Microfilament Proteins; D010744:Phosphoric Monoester Hydrolases; D034741:RNA, Small Interfering; D012367:RNA, Viral; D018091:Receptors, AMPA; C495812:Cfl1 protein, rat; C104723:glutamate receptor ionotropic, AMPA 3; C529152:SSH1 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2