title: Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex.
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.
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305, USA.
authors.forename: Martijn
authors.initials: M
authors.lastname: Gloerich
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Bianchini
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Siemers
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cohen
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305, USA.|Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA.
authors.forename: W James
authors.initials: WJ
authors.lastname: Nelson
mesh_terms: D000818:Animals; D015703:Antigens, CD; D034961:Antigens, Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D004285:Dogs; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D015703:Antigens, CD; D034961:Antigens, Nuclear; C513384:CDH1 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D011994:Recombinant Proteins