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beta 2-syntrophin a...
beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
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Mack, Natalie A. (author)
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Porter, Andrew P. (author)
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Whalley, Helen J. (author)
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Schwarz, Juliane P. (author)
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Jones, Richard C. (author)
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- Syed Khaja, Azharuddin Sajid (author)
- Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups
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- Bjartell, Anders (author)
- Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups
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Anderson, Kurt I. (author)
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Malliri, Angeliki (author)
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(creator_code:org_t)
- 2012-10-28
- 2012
- English.
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In: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 14:11, s. 1169-1180
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http://dx.doi.org/10...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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