Tankyrase regulates epithelial lumen formation via suppression of Rab11 GEFs
Open Access
- 15 June 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (7)
- https://doi.org/10.1083/jcb.202008037
Abstract
Rab11 GTPase proteins are required for cytokinesis, ciliogenesis, and lumenogenesis. Rab11a is critical for apical delivery of podocalyxin (PODXL) during lumen formation in epithelial cells. SH3BP5 and SH3BP5L are guanine nucleotide exchange factors (GEFs) for Rab11. We show that SH3BP5 and SH3BP5L are required for activation of Rab11a and cyst lumen formation. Using proximity-dependent biotin identification (BioID) interaction proteomics, we have identified SH3BP5 and its paralogue SH3BP5L as new substrates of the poly-ADP-ribose polymerase Tankyrase and the E3 ligase RNF146. We provide data demonstrating that epithelial polarity via cyst lumen formation is governed by Tankyrase, which inhibits Rab11a activation through the suppression of SH3BP5 and SH3BP5L. RNF146 reduces Tankyrase protein abundance and restores Rab11a activation and lumen formation. Thus, Rab11a activation is controlled by a signaling pathway composed of the sequential inhibition of SH3BP5 paralogues by Tankyrase, which is itself suppressed by RNF146.Keywords
Funding Information
- Canadian Institutes of Health Research
- Sir Edward Dunlop Medical Research Foundation
- MBP Excellence Ontario Student Opportunity Trust Fund
- Canada Research Chair
- Canada Foundation for Innovation
- Princess Margaret Cancer Foundation
This publication has 62 references indexed in Scilit:
- Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cellsNature, 2012
- Loss of Tankyrase-Mediated Destruction of 3BP2 Is the Underlying Pathogenic Mechanism of CherubismCell, 2011
- Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarizationProceedings of the National Academy of Sciences of the United States of America, 2011
- Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosomeProceedings of the National Academy of Sciences of the United States of America, 2011
- A molecular network for de novo generation of the apical surface and lumenNature, 2010
- Coordination of Rab8 and Rab11 in primary ciliogenesisProceedings of the National Academy of Sciences of the United States of America, 2010
- Real-time NMR Study of Guanine Nucleotide Exchange and Activation of RhoA by PDZ-RhoGEFOnline Journal of Public Health Informatics, 2010
- A Catalytic Coiled Coil: Structural Insights into the Activation of the Rab GTPase Sec4p by Sec2pMolecular Cell, 2007
- PTEN-Mediated Apical Segregation of Phosphoinositides Controls Epithelial Morphogenesis through Cdc42Cell, 2007
- The GTPase superfamily: conserved structure and molecular mechanismNature, 1991