β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity

Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify β2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight jun...

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Main Authors:	Mack, Natalie A., Porter, Andrew P., Whalley, Helen J., Schwarz, Juliane P., Jones, Richard C., Syed, Azharuddin Sajid, Bjartell, Anders, Anderson, Kurt I., Malliri, Angeliki
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498067/

id	pubmed-3498067
recordtype	oai_dc
spelling	pubmed-34980672013-05-01 β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity Mack, Natalie A. Porter, Andrew P. Whalley, Helen J. Schwarz, Juliane P. Jones, Richard C. Syed, Azharuddin Sajid Bjartell, Anders Anderson, Kurt I. Malliri, Angeliki Article Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify β2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight junction (TJ) assembly β2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that β2-syntrophin localises more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, β2-syntrophin depletion perturbs Tiam1 and Rac localisation at cell-cell junctions and causes defects in apical lumen formation. We conclude that β2-syntrophin and Par-3 finetune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polarity. 2012-10-28 2012-11 /pmc/articles/PMC3498067/ /pubmed/23103911 http://dx.doi.org/10.1038/ncb2608 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mack, Natalie A. Porter, Andrew P. Whalley, Helen J. Schwarz, Juliane P. Jones, Richard C. Syed, Azharuddin Sajid Bjartell, Anders Anderson, Kurt I. Malliri, Angeliki
spellingShingle	Mack, Natalie A. Porter, Andrew P. Whalley, Helen J. Schwarz, Juliane P. Jones, Richard C. Syed, Azharuddin Sajid Bjartell, Anders Anderson, Kurt I. Malliri, Angeliki β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
author_facet	Mack, Natalie A. Porter, Andrew P. Whalley, Helen J. Schwarz, Juliane P. Jones, Richard C. Syed, Azharuddin Sajid Bjartell, Anders Anderson, Kurt I. Malliri, Angeliki
author_sort	Mack, Natalie A.
title	β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
title_short	β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
title_full	β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
title_fullStr	β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
title_full_unstemmed	β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
title_sort	β2-syntrophin and par-3 promote an apicobasal rac activity gradient at cell-cell junctions by differentially regulating tiam1 activity
description	Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify β2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight junction (TJ) assembly β2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that β2-syntrophin localises more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, β2-syntrophin depletion perturbs Tiam1 and Rac localisation at cell-cell junctions and causes defects in apical lumen formation. We conclude that β2-syntrophin and Par-3 finetune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polarity.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498067/
_version_	1611924109785038848

β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity

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