title: A genome-wide functional screen shows MAGI-1 is an L1CAM-dependent stabilizer of apical junctions in C. elegans.
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.
authors.affiliation: Graduate Program in Genetics, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Lynch
authors.forename: Theresa
authors.initials: T
authors.lastname: Grana
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cox-Paulson
authors.forename: Annabelle
authors.initials: A
authors.lastname: Couthier
authors.forename: Michel
authors.initials: M
authors.lastname: Cameron
authors.forename: Ian
authors.initials: I
authors.lastname: Chin-Sang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pettitt
authors.forename: Jeff
authors.initials: J
authors.lastname: Hardin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D015820:Cadherins; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051178:alpha Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D034741:RNA, Small Interfering; C501528:SAX-7 protein, C elegans; C108835:afadin; D051178:alpha Catenin; D051528:Guanylate Kinases; C540161:MAGI-1 protein, C elegans