An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans
An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans
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DOI：
10.1242/dev.030759
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发表时间：
2009-03-15
期刊：
影响因子：
4.6
通讯作者：
Roy, Peter John
中科院分区：
文献类型：
--
作者：
Alexander, Mariam;Chan, Kevin Ka Ming;Roy, Peter John
胚胎神经肌肉接头的突触后膜在以后的发育过程中经历了戏剧性的扩张，以促进较大肌肉的去极化。In C.在秀丽隐杆线虫中，突触后膜位于被称为肌臂的质膜延伸的末端。膜延伸到运动轴突在幼虫发育过程中的肌肉臂的数量增加了一倍，使它们成为一个易于处理的模型来研究突触后膜扩张和引导膜延伸。为了鉴定肌臂延伸所需的基因，我们对具有较少肌臂的突变体进行了正向筛选。我们分离了14个基因中的23个突变，包括unc-40/Dcc，它编码一种跨膜受体，该受体可引导细胞迁移并响应分泌的β-6/Netrin空间线索延伸轴突。我们发现，在肌臂末端富集的α-40和功能细胞自主地指导手臂延伸到运动轴突。令人惊讶的是，E10 -6对肌肉手臂伸展的影响很小，这表明E10 -40依赖于其他空间线索来指导手臂伸展。我们提供的第一个证据表明，鸟嘌呤核苷酸交换因子<$-73/Trio，WAVE肌动蛋白聚合复合物的成员，以及粘着斑复合物的同系物可以在<$-40的下游发挥作用，以指导膜延伸。我们的工作是第一个定义定向肌膜延伸的途径，并说明轴突引导组件可以在突触后膜扩张中发挥关键作用。
The postsynaptic membrane of the embryonic neuromuscular junction undergoes a dramatic expansion during later development to facilitate the depolarization of larger muscles. In C. elegans, the postsynaptic membrane resides at the termini of plasma membrane extensions called muscle arms. Membrane extension to the motor axons during larval development doubles the number of muscle arms, making them a tractable model to investigate both postsynaptic membrane expansion and guided membrane extension. To identify genes required for muscle arm extension, we performed a forward screen for mutants with fewer muscle arms. We isolated 23 mutations in 14 genes, including unc-40/Dcc, which encodes a transmembrane receptor that guides the migration of cells and extending axons in response to the secreted UNC-6/Netrin spatial cue. We discovered that UNC-40 is enriched at muscle arm termini and functions cell-autonomously to direct arm extension to the motor axons. Surprisingly, UNC-6 is dispensable for muscle arm extension, suggesting that UNC-40 relies on other spatial cues to direct arm extension. We provide the first evidence that the guanine-nucleotide exchange factor UNC-73/Trio, members of the WAVE actin-polymerization complex, and a homolog of the focal adhesion complex can function downstream of UNC-40 to direct membrane extension. Our work is the first to define a pathway for directed muscle membrane extension and illustrates that axon guidance components can play key roles in postsynaptic membrane expansion.