Abstract
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.
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 ¿-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.
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 MAGI-1 helps to partition and maintain a stable, spatially ordered apical junction during morphogenesis.
Original language | English |
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Pages (from-to) | 1891–1899 |
Number of pages | 9 |
Journal | Current Biology |
Volume | 22 |
Issue number | 20 |
DOIs | |
Publication status | Published - 23 Oct 2012 |