A Genome-wide Functional Screen Shows MAGI-1 Is an L1CAM-Dependent Stabilizer of Apical Junctions in C. elegans

作者：Lynch Allison M; Grana Theresa; Cox Paulson Elisabeth; Couthier Annabelle; Cameron Michel; Chin Sang Ian; Pettitt Jonathan; Hardin Jeff^*

来源：Current Biology, 2012, 22(20): 1891-1899.

DOI：10.1016/j.cub.2012.08.024

Background: In multicellular organisms, cell-cell junctions are involved in many aspects of tissue morphogenesis. alpha-catenin links the cadherin-catenin complex (CCC) to the actin cytoskeleton, stabilizing cadherin-dependent adhesions. %26lt;br%26gt;Results: To identify modulators of cadherin-based cell adhesion, we conducted a genome-wide RNAi screen in C. elegans and uncovered MAGI-1, a highly conserved protein scaffold. Loss of magi-1 function in wild-type embryos results in disorganized epithelial migration and occasional morphogenetic failure. MAGI-1 physically interacts with the putative actin regulator AFD-1/afadin; knocking down magi-1 or afd-1 function in a hypomorphic alpha-catenin background leads to complete morphogenetic failure and actin disorganization in the embryonic epidermis. MAGI-1 and AFD-1 localize to a unique domain in the apical junction and normal accumulation of MAGI-1 at junctions requires SAX-7/L1CAM, which can bind MAGI-1 via its C terminus. Depletion of MAGI-1 leads to loss of spatial segregation and expansion of apical junctional domains and greater mobility of junctional proteins. %26lt;br%26gt;Conclusions: Our screen is the first genome-wide approach to identify proteins that function synergistically with the CCC during epidermal morphogenesis in a living embryo. We demonstrate novel physical interactions between MAGI-1, AFD-1/afadin, and SAX-7/L1CAM, which are part of a functional interactome that includes components of the core CCC. Our results further suggest that MAGI-1 helps to partition and maintain a stable, spatially ordered apical junction during morphogenesis.

• 出版日期2012-10-23
• 单位河北医科大学