Lim kinase regulates the development of olfactory and neuromuscular synapses.
Lim Kinase (Limk) belongs to a phylogenetically conserved family of serine/threonine kinases, which have been shown to be potent regulators of the actin cytoskeleton. Despite accumulating evidence of its biochemical actions, its in vivo function has remained poorly understood. The association of the Limk1 gene with Williams Syndrome indicates that proteins of this family play a role in the nervous system. To unravel the cellular and molecular functions of Limk, we have either knocked out or activated the Limk gene in Drosophila. At the neuromuscular junction, loss of Limk leads to enlarged terminals, while increasing the activity of Limk leads to stunted terminals with fewer synaptic boutons. In the antennal lobe, loss of Limk abolishes the ability of p21-activated kinase (Pak) to alter glomerular development. In contrast, increase in Limk function leads to ectopic glomeruli, a phenotype suppressible by the coexpression of a hyperactive Cofilin gene. These results establish Limk as a critical regulator of Cofilin function and synapse development, and a downstream effector of Pak in vivo.
Ang
Lay-Hong
LH
Department of Cell and Developmental Biology and Neuroscience Program, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
Chen
Weitao
W
Yao
Ying
Y
Ozawa
Rie
R
Tao
Enxiang
E
Yonekura
Junichiro
J
Uemura
Tadashi
T
Keshishian
Haig
H
Hing
Huey
H
D051339:Actin Depolymerizing Factors / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D004330:Drosophila / Q000196:embryology / Q000201:enzymology; D054461:Lim Kinases; D009469:Neuromuscular Junction / Q000196:embryology* / Q000201:enzymology*; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D012903:Smell / Q000502:physiology*; D013569:Synapses / Q000201:enzymology*; D054462:p21-Activated Kinases
D051339:Actin Depolymerizing Factors; D011494:Protein Kinases; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases