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SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation

The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is known to dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(3,4)P(2) and to interact with several signaling proteins though its docking functions. It has been shown to negatively regulate platelet adhesion and spreading on a fibrino...

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Autores principales: Severin, Sonia, Consonni, Alessandra, Chicanne, Gaëtan, Allart, Sophie, Payrastre, Bernard, Gratacap, Marie-Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860818/
https://www.ncbi.nlm.nih.gov/pubmed/36674478
http://dx.doi.org/10.3390/ijms24020958
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author Severin, Sonia
Consonni, Alessandra
Chicanne, Gaëtan
Allart, Sophie
Payrastre, Bernard
Gratacap, Marie-Pierre
author_facet Severin, Sonia
Consonni, Alessandra
Chicanne, Gaëtan
Allart, Sophie
Payrastre, Bernard
Gratacap, Marie-Pierre
author_sort Severin, Sonia
collection PubMed
description The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is known to dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(3,4)P(2) and to interact with several signaling proteins though its docking functions. It has been shown to negatively regulate platelet adhesion and spreading on a fibrinogen surface and to positively regulate thrombus growth. In the present study, we have investigated its role during the early phase of platelet activation. Using confocal-based morphometric analysis, we found that SHIP1 is involved in the regulation of cytoskeletal organization and internal contractile activity in thrombin-activated platelets. The absence of SHIP1 has no significant impact on thrombin-induced Akt or Erk1/2 activation, but it selectively affects the RhoA/Rho-kinase pathway and myosin IIA relocalization to the cytoskeleton. SHIP1 interacts with the spectrin-based membrane skeleton, and its absence induces a loss of sustained association of integrins to this network together with a decrease in α(IIb)β(3) integrin clustering following thrombin stimulation. This α(IIb)β(3) integrin dynamics requires the contractile cytoskeleton under the control of SHIP1. RhoA activation, internal platelet contraction, and membrane skeleton integrin association were insensitive to the inhibition of PtdIns(3,4,5)P(3) synthesis or SHIP1 phosphatase activity, indicating a role for the docking properties of SHIP1 in these processes. Altogether, our data reveal a lipid-independent function for SHIP1 in the regulation of the contractile cytoskeleton and integrin dynamics in platelets.
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spelling pubmed-98608182023-01-22 SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation Severin, Sonia Consonni, Alessandra Chicanne, Gaëtan Allart, Sophie Payrastre, Bernard Gratacap, Marie-Pierre Int J Mol Sci Article The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is known to dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(3,4)P(2) and to interact with several signaling proteins though its docking functions. It has been shown to negatively regulate platelet adhesion and spreading on a fibrinogen surface and to positively regulate thrombus growth. In the present study, we have investigated its role during the early phase of platelet activation. Using confocal-based morphometric analysis, we found that SHIP1 is involved in the regulation of cytoskeletal organization and internal contractile activity in thrombin-activated platelets. The absence of SHIP1 has no significant impact on thrombin-induced Akt or Erk1/2 activation, but it selectively affects the RhoA/Rho-kinase pathway and myosin IIA relocalization to the cytoskeleton. SHIP1 interacts with the spectrin-based membrane skeleton, and its absence induces a loss of sustained association of integrins to this network together with a decrease in α(IIb)β(3) integrin clustering following thrombin stimulation. This α(IIb)β(3) integrin dynamics requires the contractile cytoskeleton under the control of SHIP1. RhoA activation, internal platelet contraction, and membrane skeleton integrin association were insensitive to the inhibition of PtdIns(3,4,5)P(3) synthesis or SHIP1 phosphatase activity, indicating a role for the docking properties of SHIP1 in these processes. Altogether, our data reveal a lipid-independent function for SHIP1 in the regulation of the contractile cytoskeleton and integrin dynamics in platelets. MDPI 2023-01-04 /pmc/articles/PMC9860818/ /pubmed/36674478 http://dx.doi.org/10.3390/ijms24020958 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Severin, Sonia
Consonni, Alessandra
Chicanne, Gaëtan
Allart, Sophie
Payrastre, Bernard
Gratacap, Marie-Pierre
SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title_full SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title_fullStr SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title_full_unstemmed SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title_short SHIP1 Controls Internal Platelet Contraction and α(IIb)β(3) Integrin Dynamics in Early Platelet Activation
title_sort ship1 controls internal platelet contraction and α(iib)β(3) integrin dynamics in early platelet activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860818/
https://www.ncbi.nlm.nih.gov/pubmed/36674478
http://dx.doi.org/10.3390/ijms24020958
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