The ins and outs of endocytic trafficking in platelet functions

Abstract

Purpose of review While 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. This 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, as well as 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.

Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice

“…Intriguingly, we observed that cytokine reduction was due to platelet sequestration of monocyte-derived cytokines. In fact it has been long recognized that platelets can load plasma molecules (Banerjee and Whiteheart, 2017) and can selectively take up angioregulatory proteins in microscopic tumors (Klement et al, 2009). Furthermore, it has been recently shown that platelets can be loaded with ADAMTS-13 (H and I) The percentages of GFP-positive cells in the blood (H) and CD11b+Ly6C+ patrolling monocytes (I) are shown.…”

The life cycle of platelet granules

“…Synthetic pathways traffic translated proteins from ER to α -granules. The endocytic pathway enables megakaryocytes and mature platelets to acquire plasma proteins by the process of endocytosis at the plasma membrane 23 . Multiple individual proteins and protein complexes mediate trafficking of these separate pathways ( Figure 1A ).…”

“…Fibrinogen, which is internalized via integrin α IIbβ 3 , is a classic example of this route, which subsequently uses adaptor protein Disabled-2 for formation of clathrin-coated vesicles 44 , 45 . Proteins that are incorporated into platelets via pinocytosis include immunoglobulins as well as angiogenesis regulators such as VEGF, endostatin, and FGF 23 , 46 . Vesicle-associated membrane protein 3 (VAMP-3), a v-SNARE (discussed below), regulates platelet endocytosis.…”

Cellubrevin/vesicle-associated membrane protein-3–mediated endocytosis and trafficking regulate platelet functions

“…The mechanistic underpinnings of endocytosis and its importance in platelets are, however, understudied, in part because of a lack of experimental tools. 5 In this manuscript, we report the characterization of a mouse strain whose platelets are defective in endocytic trafficking of cargo.…”