MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans

Developmental Cell
Mariam AlexanderPeter J Roy

Abstract

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 MID1, 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.

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Citations

Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rei K MorikawaKazuo Emoto
Feb 18, 2012·The Journal of Biological Chemistry·Hiroaki YaguchiShigetsugu Hatakeyama
Apr 30, 2014·The Journal of Cell Biology·Cortney C WinkleStephanie L Gupton
Aug 27, 2014·The Journal of Cell Biology·Zheng WangDavid R Sherwood
Jan 11, 2016·Development, Growth & Differentiation·Evguenia IvakhnitskaiaChieh Chang
Feb 23, 2011·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Song SongXun Huang
Oct 22, 2011·Developmental Cell·Ashwin SeetharamanPeter J Roy
Nov 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tingjia LuZhiqi Xiong
Apr 2, 2016·PLoS Genetics·Alparsan AsanJames R Priess
Dec 15, 2017·Worm·Srimoyee GhoshPaul W Sternberg
Nov 9, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paige Lacy
Nov 16, 2017·Wiley Interdisciplinary Reviews. Developmental Biology·Evguenia IvakhnitskaiaChieh Chang
Jan 24, 2017·Genetics·Andrew D ChisholmWilliam G Wadsworth

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