The platelet release reaction: just when you thought... : Current Opinion in Hematology (original) (raw)

Hemostasis and thrombosis: Edited by George J. Broze Jr and Charles S. Abrams

Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA

Correspondence to Sidney W. Whiteheart, PhD, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 South Limestone, Lexington, KY 40536-0509, USA Tel: +1 859 257 4882; fax: +1 859 257 2283; e-mail: [email protected]

Abstract

Purpose of review

In response to agonists produced at vascular lesions, platelets release a host of components from their three granules: dense core, alpha, and lysosome. This releasate activates other platelets, promotes wound repair, and initiates inflammatory responses. Although widely accepted, the specific mechanisms underlying platelet secretion are only now coming to light. This review focuses on the core machinery required for platelet secretion.

Recent findings

Proteomic analyses have provided a catalog of the components released from activated platelets. Experiments using a combination of in-vitro secretion assays and knockout mice have led to assignments of both vesicle-soluble _N_-ethylmaleimide-sensitive fusion protein attachment protein receptor (v-SNARE) and target membrane SNARE to each of the three secretion events. SNARE knockout mice are also proving to be useful models for probing the role of platelet exocytosis in vivo. Other studies are beginning to identify SNARE regulators, which control when and where SNAREs interact during platelet activation.

Summary

A complex set of protein–protein interactions control the membrane fusion events required for the platelet release reaction. SNARE proteins are the core elements but the proteins that control SNARE interactions represent key points at which platelet signaling cascades could affect secretion and thrombosis.