The ins and outs of endocytic trafficking in platelet functions

Abstract

Purpose of review: Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance is poorly understood as is its mechanism. The present review discusses the current understanding of platelet endocytosis and its implications for platelet function.

Recent findings: Recent studies are beginning to identify and define the proteins that mediate platelet endocytosis. These studies have shown that platelets contain different endosomal compartments and may use multiple endocytic routes to take in circulating molecules and surface proteins. The studies have also shown that platelet endocytosis is involved in several aspects of platelet function such as signaling, spreading, and granule cargo loading.

Summary: Mechanistic studies of platelet endocytosis have shown it to be not only involved in granule cargo loading but also in various other platelet functions important for hemostasis and beyond.

Figure 1. Potential Endocytic Routes in Platelets

Cargo can enter platelets either via clathrin-dependent endocytosis, requiring GTP hydrolysis by Dynamin and using specific surface receptors (e.g., α_IIbβ₃-mediated fibrinogen entry) or via clathrin-independent endocytosis that may require Dynamin (via caveolin- or RhoA-dependent pathways) or may not (Arf6- or Cdc42-dependent pathways). Internalized cargo then transits through Rab 4 GTPase-positive early endosomes, where it can be sorted to recycling endosomes (Rab 11-positive) for return to the plasma membrane or to multivesicular bodies and ultimately into α-granules for storage (e.g., fibrinogen, vWF, thrombospondin-1). Alternatively, cargo can move into late endosomes, either directly from early endosomes or through multivesicular bodies. Cargo from late endosomes can transit into dense granules or to lysosomes where it may be degraded or stored. The complexity of these pathways in platelets has not been studied in sufficient detail.