The polarity protein Scribble positions DLC3 at adherens junctions to regulate Rho signaling
| Autor: | Simone Schmid, Monilola A. Olayioye, Mirita Franz-Wachtel, Boris Macek, Janina Hendrick, Yvonne Moeller |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RHOA PDZ domain Morphogenesis PDZ Domains Biology Ligands Cell junction Adherens junction 03 medical and health sciences Cell Adhesion Humans Molecular Biology rho-Associated Kinases Gene knockdown Scribble Polarity (international relations) Tumor Suppressor Proteins GTPase-Activating Proteins Cell Polarity Membrane Proteins Adherens Junctions Cell Biology Ligand (biochemistry) Rho signaling Cell biology HEK293 Cells 030104 developmental biology Gene Knockdown Techniques MCF-7 Cells biology.protein Caco-2 Cells rhoA GTP-Binding Protein Developmental Biology Protein Binding Signal Transduction |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.190074 |
| Popis: | The spatial regulation of cellular Rho signaling by GAP proteins is still poorly understood. By performing mass spectrometry, we here identify the polarity protein Scribble as a scaffold for the RhoGAP protein DLC3 (also known as StarD8) at cell–cell adhesions. This mutually dependent interaction is mediated by the PDZ domains of Scribble and a PDZ ligand (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 new function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells. |
| Databáze: | OpenAIRE |
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