SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility
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.
- Authors:
-
[1];
[3];
[3];
[1];
[3];
[2];
[1]
- Department of Biological Sciences, The University of Toledo, Toledo, OH
- Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI
- Department of Biochemistry, University of Iowa, Iowa City, IA
- International Center for Genetic Engineering and Biotechnology, Trieste, Italy
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source; Univ. of Toledo, OH (United States); Univ. of Michigan, Ann Arbor, MI (United States); Univ. of Iowa, Iowa City, IA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Associazione Italiana per la Ricerca sul Cancro (Italy); American Heart Association (United States)
- OSTI Identifier:
- 1564283
- Alternate Identifier(s):
- OSTI ID: 1625176
- Grant/Contract Number:
- AC02-05CH11231; 1R15CA199101; 1R21CA194776; 1R03CA197227; R01 GM112794; 18578; 15GRNT25740021
- Resource Type:
- Published Article
- Journal Name:
- Journal of Cell Biology
- Additional Journal Information:
- Journal Name: Journal of Cell Biology Journal Volume: 218 Journal Issue: 8; Journal ID: ISSN 0021-9525
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; adhesion; biochemistry; polarity
Citation Formats
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., and Garcia-Mata, Rafael. SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility. United States: N. p., 2019.
Web. doi:10.1083/jcb.201811114.
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. SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility. United States. doi:10.1083/jcb.201811114.
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., and Garcia-Mata, Rafael. Thu .
"SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility". United States. doi:10.1083/jcb.201811114.
@article{osti_1564283,
title = {SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility},
author = {Awadia, Sahezeel and Huq, Farah and Arnold, Torey R. and Goicoechea, Silvia M. and Sun, Young Joo and Hou, Titus and Kreider-Letterman, Gabriel and Massimi, Paola and Banks, Lawrence and Fuentes, Ernesto J. and Miller, Ann L. and Garcia-Mata, Rafael},
abstractNote = {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.},
doi = {10.1083/jcb.201811114},
journal = {Journal of Cell Biology},
number = 8,
volume = 218,
place = {United States},
year = {2019},
month = {6}
}
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DOI: 10.1083/jcb.201811114
DOI: 10.1083/jcb.201811114
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