Javadi, A., Deevi, R. K., Evergren, E., Blondel-Tepaz, E., Baillie, G. S. , Scott, M. G.H. and Campbell, F. C. (2017) PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex. eLife, 6, e24578. (doi: 10.7554/eLife.24578) (PMID:28749339) (PMCID:PMC5576923)
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Abstract
PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signalling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42-dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN-deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George |
| Authors: | Javadi, A., Deevi, R. K., Evergren, E., Blondel-Tepaz, E., Baillie, G. S., Scott, M. G.H., and Campbell, F. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Published Online: | 27 July 2017 |
| Copyright Holders: | Copyright © 2017 Javadi et al. |
| First Published: | First published in eLife 6:e24578 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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