TY - JOUR
T1 - SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex
AU - Chiu, Catherine W.N.
AU - Monat, Carine
AU - Robitaille, Mélanie
AU - Lacomme, Marine
AU - Daulat, Avais M.
AU - Macleod, Graham
AU - McNeill, Helen
AU - Cayouette, Michel
AU - Angers, Stéphane
N1 - Funding Information:
We wish to thank members of the Cayouette and Angers labs for discussions, and Ian Hester and Jessica Barthe for mouse colony maintenance. This work was supported by The Natural Sciences and Engineering Research Council of Canada (NSERC) (grant #386323 to S.A.), the Canadian Institutes of Health Research ( MOP-77570 to M.C.), and the W. Garfield Weston and Brain Canada Foundations . S.A. holds a Canada Research Chair in Functional Architecture of Signal Transduction, and M.C. is a Senior Fellow of the Fonds de la recherche du Québec – Santé/Fondation Antoine Turmel.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/11
Y1 - 2016/1/11
N2 - Control of cell-division orientation is integral to epithelial morphogenesis and asymmetric cell division. Proper spatiotemporal localization of the evolutionarily conserved Gαi-LGN-NuMA protein complex is critical for mitotic spindle orientation, but how this is achieved remains unclear. Here we identify Suppressor APC domain containing 2 (SAPCD2) as a previously unreported LGN-interacting protein. We show that SAPCD2 is essential to instruct planar mitotic spindle orientation in both epithelial cell cultures and mouse retinal progenitor cells in vivo. Loss of SAPCD2 randomizes spindle orientation, which in turn disrupts cyst morphogenesis in three-dimensional cultures, and triples the number of terminal asymmetric cell divisions in the developing retina. Mechanistically, we show that SAPCD2 negatively regulates the localization of LGN at the cell cortex, likely by competing with NuMA for its binding. These results uncover SAPCD2 as a key regulator of the ternary complex controlling spindle orientation during morphogenesis and asymmetric cell divisions.
AB - Control of cell-division orientation is integral to epithelial morphogenesis and asymmetric cell division. Proper spatiotemporal localization of the evolutionarily conserved Gαi-LGN-NuMA protein complex is critical for mitotic spindle orientation, but how this is achieved remains unclear. Here we identify Suppressor APC domain containing 2 (SAPCD2) as a previously unreported LGN-interacting protein. We show that SAPCD2 is essential to instruct planar mitotic spindle orientation in both epithelial cell cultures and mouse retinal progenitor cells in vivo. Loss of SAPCD2 randomizes spindle orientation, which in turn disrupts cyst morphogenesis in three-dimensional cultures, and triples the number of terminal asymmetric cell divisions in the developing retina. Mechanistically, we show that SAPCD2 negatively regulates the localization of LGN at the cell cortex, likely by competing with NuMA for its binding. These results uncover SAPCD2 as a key regulator of the ternary complex controlling spindle orientation during morphogenesis and asymmetric cell divisions.
UR - http://www.scopus.com/inward/record.url?scp=84958756300&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2015.12.016
DO - 10.1016/j.devcel.2015.12.016
M3 - Article
C2 - 26766442
AN - SCOPUS:84958756300
SN - 1534-5807
VL - 36
SP - 50
EP - 62
JO - Developmental cell
JF - Developmental cell
IS - 1
ER -