Regulation of spine morphology and synaptic function by LIMK and the actin cytoskeleton.
Filamentous actin (F-actin) is highly enriched in the dendritic spine, a specialized postsynaptic structure on which the great majority of the excitatory synapses are formed in the mammalian central nervous system (CNS). The protein kinases of the Lim-kinase (LIMK) family are potent regulators of actin dynamics in many cell types and they are abundantly expressed in the CNS, including the hippocampus. Using a combination of genetic manipulations and electrophysiological recordings in mice, we have demonstrated that LIMK-1 signaling is important in vivo in the regulation of the actin cytoskeleton, spine morphology, and synaptic function, including hippocampal long-term potentiation (LTP), a prominent form of long lasting synaptic plasticity thought to be critical to memory formation. Our results provide strong genetic evidence that LIMK and its substrate ADF/cofilin are involved in spine morphology and synaptic properties and are consistent with the notion that the Rho family small GTPases and the actin cytoskeleton are critical to spine structure and synaptic regulation.
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000502:physiology*; D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D003071:Cognition; D003599:Cytoskeleton / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism; D051345:Destrin; D054461:Lim Kinases; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D051345:Destrin; C495825:Dstn protein, mouse; D008840:Microfilament Proteins; D017470:Receptors, Glutamate; D011494:Protein Kinases; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D020743:rhoB GTP-Binding Protein