The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By mass spectrometry we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 at cell-cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZL motif in DLC3. Both Scribble depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions and is required for their functional integrity. In a 3D model of cyst development, we furthermore show that DLC3 depletion impairs polarized morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus propose a novel function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells.
%0 Journal Article
%1 Hendrick2016
%A Hendrick, Janina
%A Franz-Wachtel, Mirita
%A Moeller, Yvonne
%A Schmid, Simone
%A Macek, Boris
%A Olayioye, Monilola A.
%D 2016
%J Journal of Cell Science
%K 2016 izi olayioye
%N 19
%P 3583--3596
%R 10.1242/jcs.190074
%T The polarity protein Scribble positions DLC3 at adherens junctions to regulate Rho signaling
%U http://jcs.biologists.org/lookup/doi/10.1242/jcs.190074
%V 129
%X The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By mass spectrometry we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 at cell-cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZL motif in DLC3. Both Scribble depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions and is required for their functional integrity. In a 3D model of cyst development, we furthermore show that DLC3 depletion impairs polarized morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus propose a novel function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells.
%@ 0000000310932
@article{Hendrick2016,
abstract = {The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By mass spectrometry we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 at cell-cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZL motif in DLC3. Both Scribble depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions and is required for their functional integrity. In a 3D model of cyst development, we furthermore show that DLC3 depletion impairs polarized morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus propose a novel function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells.},
added-at = {2018-02-01T14:30:30.000+0100},
author = {Hendrick, Janina and Franz-Wachtel, Mirita and Moeller, Yvonne and Schmid, Simone and Macek, Boris and Olayioye, Monilola A.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2e07db93d2ada433ceee859333e9eba07/cristiano},
doi = {10.1242/jcs.190074},
interhash = {25f0dd78fc11f653a76167af453717b1},
intrahash = {e07db93d2ada433ceee859333e9eba07},
isbn = {0000000310932},
issn = {0021-9533},
journal = {Journal of Cell Science},
keywords = {2016 izi olayioye},
month = oct,
number = 19,
pages = {3583--3596},
pmid = {27505894},
timestamp = {2018-07-25T12:32:49.000+0200},
title = {{The polarity protein Scribble positions DLC3 at adherens junctions to regulate Rho signaling}},
url = {http://jcs.biologists.org/lookup/doi/10.1242/jcs.190074},
volume = 129,
year = 2016
}
