TY - JOUR
T1 - Junctional tumor suppressors interact with 14-3-3 proteins to control planar spindle alignment
AU - Nakajima, Yu Ichiro
AU - Lee, Zachary T.
AU - McKinney, Sean A.
AU - Swanson, Selene K.
AU - Florens, Laurence
AU - Gibson, Matthew C.
N1 - Funding Information:
This work was supported by the Stowers Institute for Medical Research and grants from National Institutes of Health (R01GM111733-01A1 to M.C. Gibson), the Naito Foundation, the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, the Astellas Foundation for Research on Metabolic Disorders, the SGH Foundation, the Uehara Memorial Foundation, the Kao Foundation for Science and Technology, the Inamori Foundation, the Takeda Science Foundation, and Japan Society for the Promotion of Science (KAKENHI grants JP17H05004 and JP17H06332 to Y. Nakajima). The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Nakajima et al.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Proper orientation of the mitotic spindle is essential for cell fate determination, tissue morphogenesis, and homeostasis. During epithelial proliferation, planar spindle alignment ensures the maintenance of polarized tissue architecture, and aberrant spindle orientation can disrupt epithelial integrity. Nevertheless, in vivo mechanisms that restrict the mitotic spindle to the plane of the epithelium remain poorly understood. Here we show that the junction-localized tumor suppressors Scribbled (Scrib) and Discs large (Dlg) control planar spindle orientation via Mud and 14-3-3 proteins in the Drosophila wing disc epithelium. During mitosis, Scrib is required for the junctional localization of Dlg, and both affect mitotic spindle movements. Using coimmunoprecipitation and mass spectrometry, we identify 14-3-3 proteins as Dlg-interacting partners and further report that loss of 14-3-3s causes both abnormal spindle orientation and disruption of epithelial architecture as a consequence of basal cell delamination and apoptosis. Combined, these biochemical and genetic analyses indicate that 14-3-3s function together with Scrib, Dlg, and Mud during planar cell division.
AB - Proper orientation of the mitotic spindle is essential for cell fate determination, tissue morphogenesis, and homeostasis. During epithelial proliferation, planar spindle alignment ensures the maintenance of polarized tissue architecture, and aberrant spindle orientation can disrupt epithelial integrity. Nevertheless, in vivo mechanisms that restrict the mitotic spindle to the plane of the epithelium remain poorly understood. Here we show that the junction-localized tumor suppressors Scribbled (Scrib) and Discs large (Dlg) control planar spindle orientation via Mud and 14-3-3 proteins in the Drosophila wing disc epithelium. During mitosis, Scrib is required for the junctional localization of Dlg, and both affect mitotic spindle movements. Using coimmunoprecipitation and mass spectrometry, we identify 14-3-3 proteins as Dlg-interacting partners and further report that loss of 14-3-3s causes both abnormal spindle orientation and disruption of epithelial architecture as a consequence of basal cell delamination and apoptosis. Combined, these biochemical and genetic analyses indicate that 14-3-3s function together with Scrib, Dlg, and Mud during planar cell division.
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U2 - 10.1083/JCB.201803116
DO - 10.1083/JCB.201803116
M3 - Article
C2 - 31088859
AN - SCOPUS:85067217942
VL - 218
SP - 1824
EP - 1838
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -