Coronin 1 Is Required for Integrin β2 Translocation in Platelets

Abstract

Remodeling of the actin cytoskeleton is one of the critical events that allows platelets to undergo morphological and functional changes in response to receptor-mediated signaling cascades. Coronins are a family of evolutionarily conserved proteins implicated in the regulation of the actin cytoskeleton, represented by the abundant coronins 1, 2, and 3 and the less abundant coronin 7 in platelets, but their functions in these cells are poorly understood. A recent report revealed impaired agonist-induced actin polymerization and cofilin phosphoregulation and altered thrombus formation in vivo as salient phenotypes in the absence of an overt hemostasis defect in vivo in a knockout mouse model of coronin 1. Here we show that the absence of coronin 1 is associated with impaired translocation of integrin β2 to the platelet surface upon stimulation with thrombin while morphological and functional alterations, including defects in Arp2/3 complex localization and cAMP-dependent signaling, are absent. Our results suggest a large extent of functional overlap among coronins 1, 2, and 3 in platelets, while aspects like integrin β2 translocation are specifically or predominantly dependent on coronin 1.

Potential Biomarkers of Acute Ischemic Stroke Etiology Revealed by Mass Spectrometry-Based Proteomic Characterization of Formalin-Fixed Paraffin-Embedded Blood Clots

“…One of the main clusters observed consisted of the protein groups coded by the genes GP9, GP1BA, MYH9, ARPC2, and CORO1C. MYH9, ARPC2, and CORO1C are involved in cytoskeletal remodeling of platelets ( 21 – 23 ). GP1BA and GP9 code for proteins that are part of a complex that works as the von Willebrand factor (vWF) receptor and mediates vWF-dependent platelet adhesion to blood vessels, which is a critical initiating event in haemostasis ( 24 ).…”

“…The proteins myosin-9, coronin-1C and actin-related protein (Arp) 2/3 complex subunit 2, for example, are in involved cytoskeletal remodeling of platelets ( 21 – 23 ), which undergo profound shape changes during activation and adhesion ( 66 ). Myosin-9 plays a crucial role in organelle distribution and F-actin organization in megakaryocytes and platelets ( 21 ) and mutations in the MYH9 gene have been related to several coagulation disorders ( 67 ).…”

“…A recent case report described a correlation between MYH9-related thrombocytopenia and Moyamoya-like vasculopathy, a disorder defined by progressive occlusion or stenosis of the intracranial distal segments of the internal carotid arteries and the arteries of the circle of Willis, provoking ischemic stroke events ( 68 ). Coronin-1C works as a regulator of the actin cytoskeleton turnover ( 69 ) together with actin-related protein 2/3 complex ( 23 , 70 ). There are several studies indicating the relevance of members of the evolutionarily conserved coronin family of proteins in stroke and thrombus formation, since they are crucial for platelet function ( 23 ), but also for controlling lipoprotein uptake and degradation in macrophages ( 71 ).…”

When Actin is Not Actin’ Like It Should: A New Category of Distinct Primary Immunodeficiency Disorders

“…Additional class I coronins may, however, compensate for the absence of coronin-1A in granulocytes, similar to platelets. Coronin-1A-deficient platelets retain the ability of the ARP2/3 complex to accumulate at the cell cortex or endosomes and phagosomes, as well as enable the formation of lamellipodia and spreading under some conditions in vitro [103]. Further investigation of the relevance of coronins for granulocyte function could elucidate the importance of this cell type in this SCID and would expand fundamental understanding of coronins in neutrophil function.…”

Editorial of Special Issue “Frontiers in the Actin Cytoskeleton”

“…Coronins 1, 2, and 3 are abundant in platelets, but their roles are poorly understood. Riley et al [6] describe the characterization of mouse platelets deficient in coronin 1 and show that the protein is dispensable for most cellular processes, most likely due to functional overlap among coronins, but is required for translocation of integrin β2 to the platelet surface upon stimulation with thrombin.…”