Lim kinase regulates the development of olfactory and neuromuscular synapses
Lim kinase regulates the development of olfactory and neuromuscular synapses
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DOI：
10.1016/j.ydbio.2006.01.030
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Hing, H
中科院分区：
文献类型：
--
作者：
Ang, LH;Weitao, C;Hing, H
Lim Kinase(LIMK)属于系统发育保守的丝氨酸/苏氨酸激酶家族，已被证明是肌动蛋白细胞骨架的有效调节因子。尽管越来越多的证据表明它的生化作用，但它在体内的功能仍然知之甚少。LIMK1基因与威廉姆斯综合征的关联表明，该家族的蛋白质在神经系统中发挥作用。为了揭示LIMK的细胞和分子功能，我们在果蝇中敲除或激活了LIMK基因。在神经肌肉连接处，LIMK的缺失会导致终末增大，而LIMK活性的增加会导致终末发育迟缓，突触突触数量减少。在触角叶中，LIMK的缺失会破坏p21激活的蛋白激酶(Pak)改变肾小球发育的能力。相反，LIMK功能的增加会导致异位肾小球，这种表型可以通过高活性的cofilin基因的共表达来抑制。这些结果证实LIMK是COFILIN功能和突触发育的关键调节因子，也是体内PAK的下游效应器。(C)2006 Elsevier Inc.保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.