Journal
JOURNAL OF CELL BIOLOGY
Volume 218, Issue 6, Pages 1824-1838Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201803116
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Funding
- Stowers Institute for Medical Research
- National Institutes of Health [R01GM111733-01A1]
- Naito Foundation
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Astellas Foundation for Research on Metabolic Disorders
- SGH Foundation
- Uehara Memorial Foundation
- Kao Foundation for Science and Technology
- Inamori Foundation
- Takeda Science Foundation
- Japan Society for the Promotion of Science (KAKENHI) [JP17H05004, JP17H06332]
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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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