Abnormal long-lasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3.
Mutations in the Pak3 gene lead to nonsyndromic mental retardation characterized by selective deficits in cognition. However, the underlying mechanisms are yet to be elucidated. We report here that the knock-out mice deficient in the expression of p21-activated kinase 3 (PAK3) exhibit significant abnormalities in synaptic plasticity, specifically hippocampal late-phase long-term potentiation, and deficiencies in learning and memory. A dramatic reduction in the active form of transcription factor cAMP-responsive element-binding protein in the knock-out mice implicates a novel signaling mechanism by which PAK3 and Rho signaling regulate synaptic function and cognition.
Meng
Jinsong
J
The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
Meng
Yanghong
Y
Hanna
Amanda
A
Janus
Christopher
C
Jia
Zhengping
Z
D000818:Animals; D001362:Avoidance Learning; D001923:Brain Chemistry; D003072:Cognition Disorders / Q000235:genetics*; D003214:Conditioning, Classical; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D003712:Dendrites / Q000648:ultrastructure; D006624:Hippocampus / Q000737:chemistry / Q000503:physiopathology*; D008607:Intellectual Disability / Q000235:genetics*; D007859:Learning Disabilities / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000648:ultrastructure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000502:physiology
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; C515912:Pak3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins