Title
Vimentin tunes cell migration on collagen by controlling !1 integrin activation and clustering
ORCID
Alison E. Patteson: 0000-0002-4004-1734
Document Type
Article
Date
Spring 3-29-2021
Keywords
PAK1, Talin, Paxillin, Vimentin, β1 integrin, Cell migration
Language
English
Funder(s)
Canadian Institutes of Health Research (CIHR) grant, Canada Research Chairs
Funding ID
MOP-416228, C.A.M.
Acknowledgements
The authors thank Joao Bronze de Firmino from the imaging facility in the Faculty of Dentistry, University of Toronto for help with developing the Fiji macro and the quantification of β1 integrin distribution. The authors thank the SPARC BioCentre - Molecular Analysis, The Hospital for Sick Children, Toronto, Canada, for assistance with mass spectrometry.
Official Citation
Zofia Ostrowska-Podhorodecka, Isabel Ding, Wilson Lee, Jelena Tanic, Sevil Abbasi, Pamma D. Arora, Richard S. Liu, Alison E. Patteson, Paul A. Janmey, Christopher A. McCulloch; Vimentin tunes cell migration on collagen by controlling β1 integrin activation and clustering. J Cell Sci 15 March 2021; 134 (6): jcs254359. doi: https://doi.org/10.1242/jcs.254359
Disciplines
Physics
Description/Abstract
Vimentin is a structural protein that is required for mesenchymal cell migration and directly interacts with actin, β1 integrin and paxillin. We examined how these interactions enable vimentin to regulate cell migration on collagen. In fibroblasts, depletion of vimentin increased talin-dependent activation of β1 integrin by more than 2-fold. Loss of vimentin was associated with reduction of β1 integrin clustering by 50% and inhibition of paxillin recruitment to focal adhesions by more than 60%, which was restored by vimentin expression. This reduction of paxillin was associated with 65% lower Cdc42 activation, a 60% reduction of cell extension formation and a greater than 35% decrease in cell migration on collagen. The activation of PAK1, a downstream effector of Cdc42, was required for vimentin phosphorylation and filament maturation. We propose that vimentin tunes cell migration through collagen by acting as an adaptor protein for focal adhesion proteins, thereby regulating β1 integrin activation, resulting in well-organized, mature integrin clusters.
Recommended Citation
Zofia Ostrowska-Podhorodecka, Isabel Ding, Wilson Lee, Jelena Tanic, Sevil Abbasi, Pamma D. Arora, Richard S. Liu, Alison E. Patteson, Paul A. Janmey, Christopher A. McCulloch; Vimentin tunes cell migration on collagen by controlling β1 integrin activation and clustering. J Cell Sci 15 March 2021; 134 (6): jcs254359. doi: https://doi.org/10.1242/jcs.254359
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
