MADD-2, a Homolog of the Opitz Syndrome Protein MID1, Regulates Guidance to the Midline through UNC-40 in Caenorhabditis elegans
MADD-2, a Homolog of the Opitz Syndrome Protein MID1, Regulates Guidance to the Midline through UNC-40 in Caenorhabditis elegans
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DOI：
10.1016/j.devcel.2010.05.016
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发表时间：
2010-06-15
影响因子：
11.8
通讯作者：
Roy, Peter J.
中科院分区：
文献类型：
--
作者：
Alexander, Mariam;Selman, Guillermo;Roy, Peter J.
秀丽隐杆线虫的身体肌肉将称为肌臂的质膜延伸至中线运动轴突，形成神经肌肉接头的突触后膜。通过筛选肌臂发育缺陷（Madd）突变体，我们之前发现UNC-40/DCC引导受体通过Rho-GEF UNC-73指导肌臂延伸。在这里，我们描述了通过突变体筛选鉴定出的一个名为 madd-2 的基因，并表明它在 UNC-40 途径中发挥作用。 MADD-2 是一种 C1-TRIM 蛋白，是人类 MIDI 的同源物，其突变会导致 Opitz 综合征。我们证明 MADD-2 可以自主地使细胞发挥作用，将肌肉和轴突延伸到蠕虫的腹侧中线。我们的结果表明，MADD-2 可能通过促进 UNC-40 和 UNC-73 之间的相互作用来增强 UNC-40 途径活性。 MADD-2 和 MID1 突变产生的类似表型表明 C1-TRIM 蛋白可能在中线发育事件中具有保守的生物学作用。
The body muscles of Caenorhabditis elegans extend plasma membrane extensions called muscle arms to the midline motor axons to form the postsynaptic membrane of the neuromuscular junction. Through a screen for muscle arm development defective (Madd) mutants, we previously discovered that the UNC-40/DCC guidance receptor directs muscle arm extension through the Rho-GEF UNC-73. Here, we describe a gene identified through our mutant screen called madd-2, and show that it functions in an UNC-40 pathway. MADD-2 is a C1-TRIM protein and a homolog of human MIDI, mutations in which cause Opitz Syndrome. We demonstrate that MADD-2 functions cell autonomously to direct muscle and axon extensions to the ventral midline of worms. Our results suggest that MADD-2 may enhance UNC-40 pathway activity by facilitating an interaction between UNC-40 and UNC-73. The analogous phenotypes that result from MADD-2 and MID1 mutations suggest that C1-TRIM proteins may have a conserved biological role in midline-oriented developmental events.