T1 - Protein synthesis by platelets
Synthesis of platelet protein in a cellâfree system
Discovery of synthesis of Bcl-3 by activated platelets sparked a search for the identities of other protein products, yielding IL-1β and TF. It also led to the unexpected discovery that their synthesis is preceded by signal-dependent cytoplasmic splicing of IL-1β and TF pre-mRNAs, yielding mature transcripts that are translated into precursor (IL-1β) and active (TF) proteins.,, This identified a novel mechanism not previously recognized in activated mammalian cells. The splicing capacities of activated platelets are intricate and will be reviewed separately. Signal-dependent splicing, together with the mTOR-dependent translational control mechanism and other regulatory pathways discussed here, indicate that platelets have unexpected diversity in posttranscriptional control. Previous and ongoing studies add to this conclusion and suggest that platelets may also use ribosomal “stalling” or polypeptide termination, participation of micro RNAs (Denis MM, Trask B, Schwertz H, Weyrich AS, Zimmerman GA, 2004) and, potentially, other modes of control. Diverse mechanisms of this sort are now emerging as important regulators of cell- and locale-selective mRNA translation and protein expression., Thus the findings to date indicate that platelets have a rich and varied repertoire of posttranscriptional pathways that are only now being revealed.
Protein synthesis in maturing human platelets
Other proteins are also reported to be synthesized by activated human platelets, although in some cases the control mechanisms have not been explored. These include plasminogen activator inhibitor (PAI) 1, tetrahydrobiopterin, cyclo-oxygenase-1, and the SVCT2 ascorbate transporter.– There is also evidence that the inducible isoform of nitric oxide synthase is produced in activated platelets, and that apoptotic proteins may be synthesized as platelets age (reviewed in reference). As noted, experiments using radiolabeled amino acid incorporation and electrophoretic separation of newly synthesized proteins indicate that there are many other protein products, with preliminary identification of some of these in progress.