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.

Details

Title
The membrane-associated fraction of cyclase associate protein 1 translocates to the cytosol upon platelet stimulation
Author
Joshi, Pooja 1 ; Riley, David R J 2 ; Khalil, Jawad S 2 ; Xiong, Huajiang 3 ; Ji, Wei 1 ; Rivero, Francisco 2   VIAFID ORCID Logo 

1  School of Life Science and Technology, Changchun University of Science and Technology, Changchun, Jilin, China; Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, Hull, UK 
2  Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Faculty of Health Sciences, University of Hull, Hull, UK 
3  Department of Biochemistry, University of Oxford, Oxford, UK 
Pages
1-12
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-29151-w
ProQuest document ID
2071157352
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.