Abstract

The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

Highlights

  • Platelets are small, anucleate blood cells derived from bone marrow megakaryocytes

  • Chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release

  • This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems

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Summary

INTRODUCTION

Anucleate blood cells derived from bone marrow megakaryocytes They are best known for their central role in maintaining the integrity of the vasculature (hemostasis) and for their pathological role in clotting arteries and veins (thrombosis) during myocardial infarction, stroke, peripheral vascular disease, and deep vein thrombosis. Despite the functional importance of platelet granule secretion in maintaining vascular integrity and promoting host defense, the molecular basis of platelet granule secretion remained poorly studied until the late 1990s, despite transformative advances in secretion biology that had occurred over the preceding decade (Rothman and Orci, 1992; Sollner et al, 1993). Proteomic studies suggest that chromaffin large dense-core vesicles (LDCVs) contain several major constituents of α-granules that can act in the vasculature, including platelet basic protein precursor, TGF-β, collagen isoforms, and metalloproteases (Table 2) (Wegrzyn et al, 2010). Large aggregates of chromogranin A require complete fusion to facilitate release (Perrais et al, 2004; Felmy, 2007)

Dense granules
Findings
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