Recent studies have demonstrated that mammalian homologues of Drosophila transient receptor
potential (TRP) channels are widely expressed in human platelets. Occupation of G protein-coupled receptors
by agonists results in activation of these channels, which results in Na+ and Ca2+ entry. Canonical or classic
TRP (TRPC) family members have been reported to associate with different Ca2+-handling proteins, including
the type II inositol 1,4,5-trisphosphate receptor, the endoplasmic reticulum Ca2+ sensor STIM1 (STromal
Interaction Molecule-1) or the Ca2+ permeable channel Orai1. The dynamic interaction of TRPC channels with
the above mentioned proteins has been found to be important for both store-operated and capacitative Ca2+
entry, as well as for non-capacitative Ca2+ influx. The former is a major mechanism for Ca2+ entry in human
platelets. This mechanism, activated by a reduction in the concentration of free Ca2+ in the intracellular stores,
results in the formation of signaling complexes involving STIM proteins, Orai1, Orai2, TRPC1 and TRPC6.
There is a growing body of evidence supporting that Ca2+ signaling dysfunction plays an important role in the
pathogenesis of several platelet-linked disorders, including those associated to type 2 diabetes mellitus.
Abnormal Ca2+ signals in response to physiological agonists have been associated to platelet hyperactivity.
The expression of several TRPCs, STIM1 and Orai1, as well as their interaction, has been reported to be
altered in platelets from type 2 diabetic patients, which results in attenuated capacitative Ca2+ entry but
enhanced non-capacitative Ca2+ influx; thus suggesting a role for Ca2+ handling proteins, including TRPs, in
the pathomechanism of diabetic complications.
Keywords: Inositol 1, 4, 5-trisphosphate receptors, Orai, platelets, STIM, TRP, Drosophila melanogaster, photoreception, canonical, ankyrin, vanilloid, melastatin, mucolipin, polycystin, protein-protein interaction, protein-ligand interaction
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