Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex

Nat Commun. 2017 Jan 3;8:13996. doi: 10.1038/ncomms13996.

Abstract

Both cell-cell adhesion and oriented cell division play prominent roles in establishing tissue architecture, but it is unclear how they might be coordinated. Here, we demonstrate that the cell-cell adhesion protein E-cadherin functions as an instructive cue for cell division orientation. This is mediated by the evolutionarily conserved LGN/NuMA complex, which regulates cortical attachments of astral spindle microtubules. We show that LGN, which adopts a three-dimensional structure similar to cadherin-bound catenins, binds directly to the E-cadherin cytosolic tail and thereby localizes at cell-cell adhesions. On mitotic entry, NuMA is released from the nucleus and competes LGN from E-cadherin to locally form the LGN/NuMA complex. This mediates the stabilization of cortical associations of astral microtubules at cell-cell adhesions to orient the mitotic spindle. Our results show how E-cadherin instructs the assembly of the LGN/NuMA complex at cell-cell contacts, and define a mechanism that couples cell division orientation to intercellular adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Nuclear / chemistry*
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism
  • Binding Sites
  • Cadherins / chemistry*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Communication
  • Cell Division
  • Cell Line
  • Dogs
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Madin Darby Canine Kidney Cells
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Models, Molecular
  • Nuclear Matrix-Associated Proteins / chemistry*
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure

Substances

  • Antigens, CD
  • Antigens, Nuclear
  • CDH1 protein, human
  • Cadherins
  • GPSM2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins
  • Recombinant Proteins