Posor, York;
Kampyli, Charis;
Bilanges, Benoit;
Ganguli, Sushila;
Koch, Philipp A;
Wallroth, Alexander;
Morelli, Daniele;
... Vanhaesebroeck, Bart; + view all
(2022)
Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover.
Developmental Cell
10.1016/j.devcel.2022.06.011.
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Abstract
Focal adhesions are multifunctional organelles that couple cell-matrix adhesion to cytoskeletal force transmission and signaling and to steer cell migration and collective cell behavior. Whereas proteomic changes at focal adhesions are well understood, little is known about signaling lipids in focal adhesion dynamics. Through the characterization of cells from mice with a kinase-inactivating point mutation in the class II PI3K-C2β, we find that generation of the phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2) membrane lipid promotes focal adhesion disassembly in response to changing environmental conditions. We show that reduced growth factor signaling sensed by protein kinase N, an mTORC2 target and effector of RhoA, synergizes with the adhesion disassembly factor DEPDC1B to induce local synthesis of PtdIns(3,4)P2 by PI3K-C2β. PtdIns(3,4)P2 then promotes turnover of RhoA-dependent stress fibers by recruiting the PtdIns(3,4)P2-dependent RhoA-GTPase-activating protein ARAP3. Our findings uncover a pathway by which cessation of growth factor signaling facilitates cell-matrix adhesion disassembly via a phosphoinositide lipid switch.
| Type: | Article |
|---|---|
| Title: | Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2022.06.011 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2022.06.011 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | ARAP3, DEPDC1B, PKN2, RhoA signaling, cell migration, class II PI3K, focal adhesion, lipid switch, phosphatidylinositol-3,4-bisphosphate, phosphoinositide |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10152024 |
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