Platelet Membrane Transporters in Health and Disease: Basic Biology and Clinical Relevance

Platelet surface adhesion receptors and intracellular signaling proteins have been the focus of platelet research for decades, with the aim of understanding how they contribute to hemostatic and thrombotic functions. However, membrane transporters and their respective roles in platelets and megakaryocytes have received relatively little attention, despite their importance for cellular regulation. Platelets harbor members of two principal structurally dissimilar large families of transporters differing in their energy source: ABC (ATP-binding cassette) transporter family and the solute carrier (SLC) family. Family members comprise integral membrane proteins that control the uptake, distribution and excretion of a variety of nutrients and metabolites, lipids, iron and drugs across concentration gradients, thereby exerting significant influence over cellular metabolism and platelet activation. In addition to transporters found in the plasma membrane, platelet transporters may also localize to lysosomal, mitochondrial and secretion granule membranes or to additional organelles. Interestingly, the impact of platelet transporters does not appear to be limited to canonical platelet functions but may extend to recently established platelet interactions with immune cells and selected tissues, with repercussions on health and disease. More recently, members of these two families have been recognized as modulators of drug efficacy and proposed as therapeutic targets. In this review we describe transporter structure, corresponding molecular mechanisms of cargo transport, functional significance, and transporter regulation, within a platelet framework.