Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex
Gloerich, Martijn; Bianchini, Julie M.; Siemers, Kathleen A.; Cohen, Daniel J.; Nelson, W. James
(2017) Nature Communications [E], volume 8
(Article)
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,
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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.
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Keywords: Animals, Antigens, CD, Antigens, Nuclear/chemistry, Binding Sites, Cadherins/chemistry, Cell Adhesion, Cell Communication, Cell Cycle Proteins, Cell Division, Cell Line, Dogs, Drosophila melanogaster/cytology, Epithelial Cells/metabolism, Gene Expression, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins/chemistry, Madin Darby Canine Kidney Cells, Microtubules/metabolism, Models, Molecular, Nuclear Matrix-Associated Proteins/chemistry, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Recombinant Proteins/chemistry, Spindle Apparatus/metabolism, General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy, Journal Article
ISSN: 2041-1723
Publisher: Nature Publishing Group
(Peer reviewed)