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J Cell Biol. 2019 Jun 3;218(6):1824-1838. doi: 10.1083/jcb.201803116. Epub 2019 May 14.

Junctional tumor suppressors interact with 14-3-3 proteins to control planar spindle alignment.

Author information

1
Stowers Institute for Medical Research, Kansas City, MO yuichiro.nakajima.d2@tohoku.ac.jp.
2
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.
3
Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
4
Stowers Institute for Medical Research, Kansas City, MO.
5
Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS.

Abstract

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.

PMID:
31088859
PMCID:
PMC6548121
[Available on 2019-12-28]
DOI:
10.1083/jcb.201803116

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