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Johnson, Robert T., Wostear, Finn, Solanki, Reesha, Steward, Oliver, Bradford, Alice, Morris, Christopher 
ORCID: https://orcid.org/0000-0002-7703-4474, Bidula, Stefan ORCID: https://orcid.org/0000-0002-3790-7138 and Warren, Derek T.
(2024)
A microtubule stability switch alters isolated vascular smooth muscle Ca2+ flux in response to matrix rigidity.
Journal of Cell Science, 137 (21).
ISSN 0021-9533
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Abstract
During ageing, the extracellular matrix of the aortic wall becomes more rigid. In response, vascular smooth muscle cells (VSMCs) generate enhanced contractile forces. Our previous findings demonstrate that VSMC volume is enhanced in response to increased matrix rigidity, but our understanding of the mechanisms regulating this process remain incomplete. In this study, we show that microtubule stability in VSMCs is reduced in response to enhanced matrix rigidity via Piezo1-mediated Ca2+ influx. Moreover, VSMC volume and Ca2+ flux is regulated by microtubule dynamics; microtubule-stabilising agents reduced both VSMC volume and Ca2+ flux on rigid hydrogels, whereas microtubule-destabilising agents increased VSMC volume and Ca2+ flux on pliable hydrogels. Finally, we show that disruption of the microtubule deacetylase HDAC6 uncoupled these processes and increased α-tubulin acetylation on K40, VSMC volume and Ca2+ flux on pliable hydrogels, but did not alter VSMC microtubule stability. These findings uncover a microtubule stability switch that controls VSMC volume by regulating Ca2+ flux. Taken together, these data demonstrate that manipulation of microtubule stability can modify VSMC response to matrix stiffness.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability statement: All relevant data can be found within the article and its supplementary information. Funding Information: This work was funded by a Biotechnology and Biological Sciences Research Council Research Grant (BB/T007699/1) awarded to D.T.W. and UKRI Biotechnology and Biological Sciences Research Council Norwich Research Park Doctoral Training Partnership PhD Studentships awarded to F.W. (BB/T008717/1) and A.B. (BB/T008717/1). R.S. was funded by a University of East Anglia Science Faculty PhD Studentship. Open Access funding provided by University of East Anglia. Deposited in PMC for immediate release. |
| Uncontrolled Keywords: | ca flux,matrix rigidity,microtubule,smooth muscle cell,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307 |
| Faculty \ School: | Faculty of Science > School of Chemistry (former - to 2024) Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 28 Nov 2024 01:37 |
| Last Modified: | 02 Dec 2024 01:45 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97815 |
| DOI: | 10.1242/jcs.262310 |
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