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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD
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Antigens, Nuclear / chemistry*
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Antigens, Nuclear / genetics
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Antigens, Nuclear / metabolism
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Binding Sites
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Cadherins / chemistry*
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Cadherins / genetics
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Cadherins / metabolism
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Cell Adhesion
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Cell Communication
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Cell Cycle Proteins
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Cell Division
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Cell Line
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Dogs
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Drosophila melanogaster / cytology
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Drosophila melanogaster / metabolism
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Epithelial Cells / metabolism*
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Epithelial Cells / ultrastructure
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Gene Expression
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HEK293 Cells
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry*
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Madin Darby Canine Kidney Cells
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Microtubules / metabolism*
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Microtubules / ultrastructure
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Models, Molecular
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Nuclear Matrix-Associated Proteins / chemistry*
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Nuclear Matrix-Associated Proteins / genetics
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Nuclear Matrix-Associated Proteins / metabolism
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Protein Binding
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Protein Interaction Domains and Motifs
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Spindle Apparatus / metabolism*
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Spindle Apparatus / ultrastructure
Substances
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Antigens, CD
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Antigens, Nuclear
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CDH1 protein, human
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Cadherins
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Cell Cycle Proteins
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GPSM2 protein, human
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Intracellular Signaling Peptides and Proteins
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NUMA1 protein, human
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Nuclear Matrix-Associated Proteins
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Recombinant Proteins