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

Curr Biol. 2012 Oct 23;22(20):1891-9. doi: 10.1016/j.cub.2012.08.024. Epub 2012 Sep 13.

Abstract

Background: In multicellular organisms, cell-cell junctions are involved in many aspects of tissue morphogenesis. α-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 α-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 that MAGI-1 helps to partition and maintain a stable, spatially ordered apical junction during morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Adherens Junctions / genetics
  • Adherens Junctions / metabolism*
  • Adherens Junctions / ultrastructure
  • Animals
  • Cadherins
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Neural Cell Adhesion Molecules / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • alpha Catenin / metabolism

Substances

  • Cadherins
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • RNA, Small Interfering
  • SAX-7 protein, C elegans
  • afadin
  • alpha Catenin
  • Guanylate Kinases
  • MAGI-1 protein, C elegans