Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1).
The Rho family small GTPases are critically involved in the regulation of spine and synaptic properties, but the underlying mechanisms are poorly defined. We took genetic approaches to create and analyze knockout mice deficient in the expression of the protein kinase PAK1 that is directly associated with and activated by the Rho GTPases. We demonstrated that while these knockout mice were normal in both basal and presynaptic function, they were selectively impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Consistent with the electrophysiological deficits, the PAK1 knockout mice showed changes in the actin cytoskeleton and the actin binding protein cofilin. These results indicate that PAK1 is critical in hippocampal synaptic plasticity via regulating cofilin activity and the actin cytoskeleton.
Asrar
Suhail
S
Neurosciences and Mental Health, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Meng
Yanghong
Y
Zhou
Zikai
Z
Todorovski
Zarko
Z
Huang
Wayne Wenyin
WW
Jia
Zhengping
Z
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001703:Biophysics; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000648:ultrastructure; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000648:ultrastructure; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000172:deficiency / Q000502:physiology*
D051339:Actin Depolymerizing Factors; D000199:Actins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C515905:Pak1 protein, mouse; D054462:p21-Activated Kinases