| Autor: |
Javadi, Arman, Deevi, Ravi K., Evergren, Emma, Blondel-Tepaz, Elodie, Baillie, George S., Scott, Mark G. H., Campbell, Frederick C. |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Zdroj: |
Javadi, A, Deevi, R K, Evergren, E, Blondel-Tepaz, E, Baillie, G S, Scott, M G H & Campbell, F C 2017, ' PTEN 1 controls glandular morphogenesis through a juxtamembrane 2 β-Arrestin1/ARHGAP21 scaffolding complex ', eLife, vol. 6, no. e24578 . https://doi.org/10.7554/eLife.24578 |
| DOI: |
10.7554/eLife.24578 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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