beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity

Mack, Natalie A. (author)

Porter, Andrew P. (author)

Whalley, Helen J. (author)

Schwarz, Juliane P. (author)

Jones, Richard C. (author)

Syed Khaja, Azharuddin Sajid (author): Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups

Bjartell, Anders (author): Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups

Anderson, Kurt I. (author)

Malliri, Angeliki (author)

(creator_code:org_t)

2012-10-28
2012
English.
In: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 14:11, s. 1169-1180

Related links:: http://dx.doi.org/10...; show more...; https://europepmc.or...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

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 beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-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 beta 2-syntrophin localizes 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, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy.

By the author/editor: Mack, Natalie A.; Porter, Andrew P ...; Whalley, Helen J ...; Schwarz, Juliane ...; Jones, Richard C ...; Syed Khaja, Azha ...; show more...; Bjartell, Anders; Anderson, Kurt I ...; Malliri, Angelik ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

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