A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of apical junctions in C. elegans

Allison Lynch, Theresa Grana, Elisabeth Cox, Annabelle Couthier, Michel Cameron, Ian Chin-Sang, Jonathan Pettitt, Jeff Hardin

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 languageEnglish
Pages (from-to)1891–1899
Number of pages9
JournalCurrent Biology
Volume22
Issue number20
DOIs
Publication statusPublished - 23 Oct 2012

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