Abstract
Rapid reorganization of the actin cytoskeleton in response to receptor-mediated signaling cascades allows platelets to transition from a discoid shape to a flat spread shape upon adhesion to damaged vessel walls. Coronins are conserved regulators of the actin cytoskeleton turnover but they also participate in signaling events. To gain a better picture of their functions in platelets we have undertaken a biochemical and immunocytochemical investigation with a focus on Coro1. We found that class I coronins Coro1, 2 and 3 are abundant in human and mouse platelets whereas little Coro7 can be detected. Coro1 is mainly cytosolic, but a significant amount associates with membranes in an actin-independent manner and does not translocate from or to the membrane fraction upon exposure to thrombin, collagen or prostacyclin. Coro1 rapidly translocates to the Triton insoluble cytoskeleton upon platelet stimulation with thrombin or collagen. Coro1, 2 and 3 show a diffuse cytoplasmic localization with discontinuous accumulation at the cell cortex and actin nodules of human platelets, where all three coronins colocalize. Our data are consistent with a role of coronins as integrators of extracellular signals with actin remodeling and suggests a high extent of functional overlap among class I coronins in platelets.
Highlights
Platelets are anucleate fragments of megakaryocytes that play pivotal roles in hemostasis, thrombosis, wound healing and immunological processes
We present immunological evidence of the presence of members of the coronin family in human and mouse platelets
Our results are in very broad agreement with data from proteomics and transcriptomic studies (Supplemental Table 1 and 2), with the caveat that western immunoblot results are not suitable for quantitative comparisons due to the fact that all the antibodies we have used were raised against fragments of human coronins; we expect them to have different affinities for the corresponding mouse protein
Summary
Platelets are anucleate fragments of megakaryocytes that play pivotal roles in hemostasis, thrombosis, wound healing and immunological processes. While in circulation they have a characteristic discoid shape, but are capable of undergoing profound changes upon adhesion to damaged blood vessel walls, transitioning to a spherical shape that extends filopodia and lamellipodia as the cell spreads and flattens [1]. This process is accompanied by secretion of granules and activation of integrins that support and consolidate the formation of a platelet aggregate. A plethora of proteins with various biochemical activities is responsible for the dynamics of actin remodeling during platelet activation, including actin nucleators like formins and the Arp2/3 complex and their regulators (WAVE, WASP), monomeric actin-binding proteins like profilin, β-thymosin and the cyclase-associated protein (CAP) and others like gelsolin, cofilin, and coronins [3,4,5]
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