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

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

doi:10.1083/JCB.201811114

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

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

Sahezeel Awadia, Farah Huq, Torey R Arnold, Silvia M Goicoechea, Young Joo Sun, Titus Hou, Gabriel Kreider-Letterman, Paola Massimi, Lawrence Banks, Ernesto J Fuentes, …

The Journal of cell biology, Vol.218(8), pp.2699-2725

08/05/2019

DOI: 10.1083/JCB.201811114

PMCID: PMC6683736

PMID: 31248911

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Abstract

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.

Actomyosin - metabolism

Adherens Junctions - metabolism

Animals

Cadherins - metabolism

Cell Polarity

Discs Large Homolog 1 Protein - chemistry

Discs Large Homolog 1 Protein - metabolism

Dogs

Embryo, Nonmammalian - metabolism

Epithelial Cells - metabolism

Guanine Nucleotide Exchange Factors - chemistry

Guanine Nucleotide Exchange Factors - metabolism

HEK293 Cells

Humans

Intercellular Junctions - metabolism

Intracellular Signaling Peptides and Proteins - metabolism

Madin Darby Canine Kidney Cells

Protein Binding

Protein Domains

Tight Junctions - metabolism

Xenopus laevis

Details

Title: Subtitle: SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility
Creators: Sahezeel Awadia - University of Toledo
Farah Huq - University of Michigan
Torey R Arnold - University of Michigan
Silvia M Goicoechea - University of Toledo
Young Joo Sun - University of Iowa
Titus Hou - University of Iowa
Gabriel Kreider-Letterman - University of Toledo
Paola Massimi - International Centre for Genetic Engineering and Biotechnology
Lawrence Banks - International Centre for Genetic Engineering and Biotechnology
Ernesto J Fuentes - University of Iowa
Ann L Miller - University of Michigan
Rafael Garcia-Mata - University of Toledo
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.218(8), pp.2699-2725
DOI: 10.1083/JCB.201811114
PMID: 31248911
PMCID: PMC6683736
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Grant note: R03 CA197227 / NCI NIH HHS R01 GM112794 / NIGMS NIH HHS R15 CA199101 / NCI NIH HHS R21 CA194776 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 08/05/2019
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984288715402771

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