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The membrane-associated fraction of cyclase associated protein 1 translocates to the cytosol upon platelet stimulation

Joshi, Pooja; Riley, David R.J.; Khalil, Jawad S.; Xiong, Huajiang; Ji, Wei; Rivero, Francisco

Authors

Pooja Joshi

David R.J. Riley

Jawad S. Khalil

Huajiang Xiong

Wei Ji

Francisco Rivero



Abstract

Platelets undergo profound shape changes upon adhesion to damaged blood vessel walls that are mediated by reorganisation of the actin cytoskeleton in response to receptor-mediated signalling cascades. The highly conserved 56 kDa multidomain cyclase associated protein 1 (CAP1) works in concert with cofilin and profilin to modulate actin filament turnover by facilitating cofilin-mediated actin filament severing and depolymerisation and catalysing profilin-mediated regeneration of actin monomers for reutilisation in growing filaments. CAP1 is abundant in platelets but its roles remain unexplored. We report that in suspended platelets CAP1 localises predominantly at the cell cortex whereas in spread platelets it is uniformly distributed in the cytoplasm, with enrichment at the cell cortex and the periphery of actin nodules. Upon subcellular fractionation most CAP1 was found cytosolic but part associated to the membrane fraction in an actin-independent manner. Interestingly, upon stimulation with thrombin a significant proportion of the membrane-associated CAP1 translocates to the cytosol. This relocalisation was prevented by prior treatment with PGI2 or the nitric oxide donor GSNO, or by inhibition of GSK3. Our results place CAP1 at a crossroad of signalling pathways that control platelet activation by contributing to actin remodelling at the cell cortex and actin nodules during platelet spreading.

Citation

Joshi, P., Riley, D. R., Khalil, J. S., Xiong, H., Ji, W., & Rivero, F. (2018). The membrane-associated fraction of cyclase associated protein 1 translocates to the cytosol upon platelet stimulation. Scientific reports, 8, https://doi.org/10.1038/s41598-018-29151-w

Journal Article Type Article
Acceptance Date Jul 3, 2018
Online Publication Date Jul 17, 2018
Publication Date Jul 17, 2018
Deposit Date Mar 18, 2020
Publicly Available Date Mar 19, 2020
Journal Scientific reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Article Number 10804
DOI https://doi.org/10.1038/s41598-018-29151-w
Keywords Actin; Extracellular signalling molecules; Lamellipodia
Public URL https://hull-repository.worktribe.com/output/918675
Publisher URL https://www.nature.com/articles/s41598-018-29151-w

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https://creativecommons.org/licenses/by/4.0/

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.





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