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

Martijn Gloerich, Julie M. Bianchini, Kathleen A. Siemers, Daniel J. Cohen, W. James Nelson

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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.

Original languageEnglish (US)
Article number13996
JournalNature communications
StatePublished - Jan 3 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology


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