SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

Awadia, Sahezeel; Huq, Farah; Arnold, Torey R.; Goicoechea, Silvia M.; Sun, Young Joo; Hou, Titus; Kreider-Letterman, Gabriel; Massimi, Paola; Banks, Lawrence; Fuentes, Ernesto J.; Miller, Ann L.; Garcia-Mata, Rafael

doi:10.1083/jcb.201811114

Title: SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility

Journal Article · 26 June 2019 · Journal of Cell Biology

DOI: https://doi.org/10.1083/jcb.201811114 · OSTI ID:1564283

; Huq, Farah; Arnold, Torey R.; Goicoechea, Silvia M.;

;

; Massimi, Paola; Banks, Lawrence;

;

The canonical Scribble polarity complex is implicated in regulation of epithelial junctions and apical polarity. Here, we show that SGEF, a RhoG-specific GEF, forms a ternary complex with Scribble and Dlg1, two members of the Scribble complex. SGEF targets to apical junctions in a Scribble-dependent fashion and functions in the regulation of actomyosin-based contractility and barrier function at tight junctions as well as E-cadherin–mediated formation of adherens junctions. Surprisingly, SGEF does not control the establishment of polarity. However, in 3D cysts, SGEF regulates the formation of a single open lumen. Interestingly, SGEF’s nucleotide exchange activity regulates the formation and maintenance of adherens junctions, and in cysts the number of lumens formed, whereas SGEF’s scaffolding activity is critical for regulation of actomyosin contractility and lumen opening. We propose that SGEF plays a key role in coordinating junctional assembly and actomyosin contractility by bringing together Scribble and Dlg1 and targeting RhoG activation to cell–cell junctions.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1564283

Alternate ID(s):: OSTI ID: 1625176

Journal Information:: Journal of Cell Biology, Journal Name: Journal of Cell Biology Journal Issue: 8 Vol. 218; ISSN 0021-9525

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Developmental capacities of benign and malignant neoplasms ofDrosophila Gateff, E.; Schneiderman, Howard A. Wilhelm Roux Archiv f�r Entwicklungsmechanik der Organismen, Vol. 176, Issue 1 https://doi.org/10.1007/BF00577830	journal	January 1974
The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions Woods, Daniel F.; Bryant, Peter J. Cell, Vol. 66, Issue 3 https://doi.org/10.1016/0092-8674(81)90009-X	journal	August 1991
Human Homolog of Disc-large Is Required for Adherens Junction Assembly and Differentiation of Human Intestinal Epithelial Cells Laprise, Patrick; Viel, Alain; Rivard, Nathalie Journal of Biological Chemistry, Vol. 279, Issue 11 https://doi.org/10.1074/jbc.M309843200	journal	December 2003
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Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis Terry, Stephen J.; Zihni, Ceniz; Elbediwy, Ahmed Nature Cell Biology, Vol. 13, Issue 2 https://doi.org/10.1038/ncb2156	journal	January 2011
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hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells Métais, Jean-Yves; Navarro, Christel; Santoni, Marie-Josée FEBS Letters, Vol. 579, Issue 17 https://doi.org/10.1016/j.febslet.2005.05.062	journal	June 2005
Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance Stevenson, B. R. The Journal of Cell Biology, Vol. 107, Issue 6 https://doi.org/10.1083/jcb.107.6.2401	journal	December 1988

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