Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice.
In vitro studies indicate a role for the LIM kinase family in the regulation of cofilin phosphorylation and actin dynamics. In addition, abnormal expression of LIMK-1 is associated with Williams syndrome, a mental disorder with profound deficits in visuospatial cognition. However, the in vivo function of this family of kinases remains elusive. Using LIMK-1 knockout mice, we demonstrate a significant role for LIMK-1 in vivo in regulating cofilin and the actin cytoskeleton. Furthermore, we show that the knockout mice exhibited significant abnormalities in spine morphology and in synaptic function, including enhanced hippocampal long-term potentiation. The knockout mice also showed altered fear responses and spatial learning. These results indicate that LIMK-1 plays a critical role in dendritic spine morphogenesis and brain function.
Program in Brain and Behavior, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
Yanghong
Y
Meng
Yu
Y
Zhang
Vitali
V
Tregoubov
Christopher
C
Janus
Luis
L
Cruz
Mike
M
Jackson
Wei Yang
WY
Lu
John F
JF
MacDonald
Jay Y
JY
Wang
Douglas L
DL
Falls
Zhengping
Z
Jia
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D051339:Actin Depolymerizing Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D003712:Dendrites / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000002:abnormalities* / Q000254:growth & development / Q000473:pathology; D054461:Lim Kinases; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000502:physiology; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009433:Neural Inhibition / Q000235:genetics; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D018980:Williams Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D051339:Actin Depolymerizing Factors; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases