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DOI: 10.1055/s-2004-833484
Change in Protein Phenotype without a Nucleus: Translational Control in Platelets
Publikationsverlauf
Publikationsdatum:
08. September 2004 (online)
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For most cells the nucleus takes center stage. Not only is it the largest organelle in eukaryotic cells, it carries most of the genome and transcription of DNA to RNA largely takes place in the nucleus. Because transcription is a major step in gene regulation, the absence of a nucleus is limiting from a biosynthetic standpoint. Consequently, the anucleate status of platelets has stereotyped it as a cell without synthetic potential. It is now clear, however, that this viewpoint is far too simplistic. In response to physiologic stimuli, platelets synthesize biologically relevant proteins that are regulated via gene expression programs at the translational level. This process does not require a nucleus; instead, it uses mRNAs and other translational factors that appear to be retained in specialized fashion as megakaryocytes generate platelets during thrombopoiesis. We highlight the molecular machinery and pathways used by platelets to translate mRNA into protein and offer insight into how these synthesized products may regulate thrombotic and inflammatory events.
KEYWORDS
Megakaryocytes - nucleus - platelets - RNA - translation
REFERENCES
- 1 Batar P AD. GL. Platelet turnover and aging. In: Michelson AD Platelets. San Diego, CA; Elsevier Science 2002: 53-64
- 2 Woulfe D, Yang J, Prevost N, O'Brien P J, Brass L. Signal transduction during the initiation, extension, and perpetuation of platelet plug formation. In: Michelson AD Platelets. San Diego, CA; Elsevier Science 2002: 197-213
- 3 Weyrich A S, Lindemann S, Zimmerman G A. The evolving role of platelets in inflammation. J Thromb Haemost. 2003; 2 1-9
- 4 Parise L V. Integrin alpha(IIb)beta(3) signaling in platelet adhesion and aggregation. Curr Opin Cell Biol. 1999; 11 597-601
- 5 Reed G L. Platelet secretion. In: Michelson AD Platelets. San Diego, CA; Elsevier Science 2002: 181-195
- 6 Italiano Jr J E, Shivdasani R A. Megakaryocytes and beyond: the birth of platelets. J Thromb Haemost. 2003; 1 1174-1182
- 7 Italiano Jr J, Hartwig J H. Megakaryocyte development and platelet formation. In: Michelson AD Platelets. San Diego, CA; Elsevier 2002: 21-35
- 8 Weyrich A S, Zimmerman G A. Evaluating the relevance of the platelet transcriptome. Blood. 2003; 102 1550-1551
- 9 Gnatenko D V, Dunn J J, McCorkle S R, Weissmann D, Perrotta P L, Bahou W F. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood. 2003; 101 2285-2293
- 10 Mathews M B, Sonenberg N, Hershey J WB. Origins and principles of translational control. In: Mathews MB, Sonenberg N, Hershey JWB Translational Control of Gene Expression. Cold Spring Harbor, NY; Cold Spring Harbor Laboratory Press 2000: 1-31
- 11 Lindemann S, McIntyre T M, Prescott S M, Zimmerman G A, Weyrich A S. Expanding the functional repertoire of platelets in thrombosis and inflammation: signal-dependent protein synthesis. In: Fitzgerald DJ, Quinn MA Platelet Function: Assessment, Diagnosis, and Treatment. Totowa, NJ; The Humana Press 2003
- 12 Lindemann S, Tolley N D, Dixon D A et al.. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol. 2001; 154 485-490
- 13 Lindemann S, Tolley N D, Eyre J R, Kraiss L W, Mahoney T M, Weyrich A S. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control. J Biol Chem. 2001; 276 33947-33951
- 14 Pabla R, Weyrich A S, Dixon D A et al.. Integrin-dependent control of translation: Engagement of integrin αIIbβ3 regulates synthesis of proteins in activated human platelets. J Cell Biol. 1999; 144 175-184
- 15 Weyrich A S, Dixon D A, Pabla R et al.. Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc Natl Acad Sci USA. 1998; 95 5556-5561
- 16 Kraiss L W, Weyrich A S, Alto N M et al.. Fluid flow activates a regulator of translation, p70/p85 s6 kinase, in human endothelial cells. Am J Physiol Heart Circ Physiol. 2000; 278 1537-1544
- 17 Mahoney T S, Weyrich A S, Dixon D A, McIntyre T, Prescott S M, Zimmerman G A. Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes. Proc Natl Acad Sci USA. 2001; 98 10284-10289
- 18 Booyse F M, Rafelson M E. Protein synthesis and platelet function. In: Johnson SA, Guest M Dynamics of thrombus formation and dissolution. Philadelphia, PA; JB Lippincott 1969: 149
- 19 Booyse F M, Hoveke T P, Rafelson M E. Studies on human platelets. II. Protein synthetic activity of various platelet populations. Biochim Biophys Acta. 1968; 157 660-663
- 20 Booyse F M, Rafelson Jr M E. Studies on human platelets. I. Synthesis of platelet protein in a cell-free system. Biochim Biophys Acta. 1968; 166 689-697
- 21 Booyse F, Rafelson Jr M E. In vitro incorporation of amino-acids into the contractile protein of human blood platelets. Nature. 1967; 215 283-284
- 22 Roth G J, Hickey M J, Chung D W, Hickstein D D. Circulating human blood platelets retain appreciable amounts of poly (a)+ RNA. Biochem Biophys Res Commun. 1989; 160 705-710
- 23 Hershey J WB, Merrick W. The pathway and mechanism of initiation of protein synthesis. In: Sonenberg N, Hershey JWB, Mathews MB Translational Control of Gene Expression. Cold Spring Harbor, NY; Cold Spring Harbor Laboratory Press 2000: 33-88
- 24 Rosenwald I B, Pechet L, Han A et al.. Expression of translation initiation factors eIF-4E and eIF-2α and a potential physiologic role of continuous protein synthesis in human platelets. Thromb Haemost. 2001; 85 142-151
- 25 Richter J D. Cytoplasmic polyadenylation in development and beyond. Microbiol Mol Biol Rev. 1999; 63 446-456
- 26 Jacobson A. Poly(A) metabolism and translation: the closed loop model. In: Hershey JWB, Mathews MB, Sonenberg N Translational Control. Cold Spring Harbor, NY; Cold Spring Harbor Laboratory Press 1996: 451-480
- 27 Sachs A. Physical and functional interactions between the mRNA cap structure and the poly(a) tail. In: Sonenberg N, Hershey JWB, Mathews MB Translational Control of Gene Expression. Cold Spring Harbor, NY; Cold Spring Harbor Laboratory Press 2000: 447-465
- 28 Sottile J, Mosher D F, Fullenweider J, George J N. Human platelets contain mRNA transcripts for platelet factor 4 and actin. Thromb Haemost. 1989; 62 1100-1102
- 29 Dixon D A, Tolley N D, Zimmerman G A. Convenient and rapid ribonuclease protection assay for use with primary cell cultures. Biotechniques. 2001; 31 992-993
- 30 Kochetov A V, Ischenko I V, Vorobiev D G et al.. Eukaryotic mRNAs encoding abundant and scarce proteins are statistically dissimilar in many structural features. FEBS Lett. 1998; 440 351-355
- 31 Papkoff J, Chen R H, Blenis J, Forsman J. P42 mitogen-activated protein kinase and p90 ribosomal S6 kinase are selectively phosphorylated and activated during thrombin-induced platelet activation and aggregation. Mol Cell Biol. 1994; 14 463-472
- 32 Nguyen Y H, Mills A A, Stanbridge E J. Assembly of the QM protein onto the 60S ribosomal subunit occurs in the cytoplasm. J Cell Biochem. 1998; 68 281-285
- 33 Kieffer N, Guichard J, Farcet J P, Vainchenker W, Breton-Gorius J. Biosynthesis of major platelet proteins in human blood platelets. Eur J Biochem. 1987; 164 189-195
- 34 Belloc F, Hourdille P, Boisseau M R, Bernard P. Protein synthesis in human platelets correlation with platelet size. Nouv Rev Fr Hematol. 1982; 24 369-373
- 35 Hesketh J, Jodar D, Johannessen A, Partridge K, Pryme I, Tauler A. Enrichment of specific mRNAs in cytoskeletal-bound and membrane-bound polysomes in Chinese hamster ovary cells. Biochem Soc Trans. 1996; 24 187S
- 36 Clark I E, Wyckoff D, Gavis E R. Synthesis of the posterior determinant nanos is spatially restricted by a novel cotranslational regulatory mechanism. Curr Biol. 2000; 10 1311-1314
- 37 Houng A K, Maggini L, Clement C Y, Reed G L. Identification and structure of activated-platelet protein-1, a protein with RNA-binding domain motifs that is expressed by activated platelets. Eur J Biochem. 1997; 243 209-218
- 38 Gingras A-C, Raught B, Sonenberg N. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem. 1999; 68 913-963
- 39 Hefner Y, Borsch-Haubold A G, Murakami M et al.. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J Biol Chem. 2000; 275 37542-37551
- 40 Gingras A C, Kennedy S G, O’Leary M A, Sonenberg N, Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the AKT(PKB) signaling pathway. Genes Dev. 1998; 12 502-513
- 41 Singh J, Kaul D. RNA-mediated regulation of receptor-ck gene in human platelets. Mol Cell Biochem. 1997; 173 189-192
- 42 Lemaitre D, Vericel E, Polette A, Lagarde M. Effects of fatty acids on human platelet glutathione peroxidase: Possible role of oxidative stress. Biochem Pharmacol. 1997; 53 479-486
- 43 McBane II R D, Ford M A, Karnicki K, Stewart M, Owen W G. Fibrinogen, fibrin and crosslinking in aging arterial thrombi. Thromb Haemost. 2000; 84 83-87
- 44 Wysokinski W, McBane R, Chesebro J H, Owen W G. Reversibility of platelet thrombosis in vivo. Quantitative analysis in porcine carotid arteries. Thromb Haemost. 1996; 76 1108-1113
- 45 Sakata K, Shigemasa K, Uebaba Y, Nagai N, Ohama K. Expression of matrix metalloproteinases-2 and -9 by cells isolated from the peritoneal fluid of women with ovarian carcinoma. Acta Cytol. 2002; 46 697-703
- 46 Owen W G, Bichler J, Ericson D, Wysokinski W. Gating of thrombin in platelet aggregates by po2-linked lowering of extracellular Ca2+ concentration. Biochemistry. 1995; 34 9277-9281
- 47 Abraham R T, Wiederrecht G J. Immunopharmacology of rapamycin. Annu Rev Immunol. 1996; 14 483-510
- 48 Sousa J E, Costa M A, Abizaid A et al.. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation. 2001; 103 192-195
- 49 Kaplanski G, Porat R, Aiura K, Erban J K, Gelfand J A, Dinarello C A. Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event. Blood. 1993; 81 2492-2495
- 50 Hawrylowicz C M, Santoro S A, Platt F M, Unanue E R. Activated platelets express IL-1 activity. J Immunol. 1989; 143 4015-4018
- 51 Duquette M, Laneuville O. Translational regulation of prostaglandin endoperoxide h synthase-1 mRNA in megakaryocytic MEG-01 cells. Specific protein binding to a conserved 20-nucleotide cis element in the 3′-untranslated region. J Biol Chem. 2002; 277 44631-44637
- 52 Kunicki T J, Newman P J. Synthesis of analogs of human platelet membrane glycoprotein IIb-IIIa complex by chicken peripheral blood thrombocytes. Proc Natl Acad Sci USA. 1985; 82 7319-7323
- 53 Waggoner S A, Liebhaber S A. Regulation of alpha-globin mRNA stability. Exp Biol Med (Maywood). 2003; 228 387-395
- 54 Knowles R B, Sabry J H, Martone M E et al.. Translocation of RNA granules in living neurons. J Neurosci. 1996; 16 7812-7820
Andrew S WeyrichPh.D.
Human Molecular Biology and Genetics, Bldg. 533
Rm. 4220, University of Utah
Salt Lake City, Utah 84112
eMail: andy.weyrich@hmbg.utah.edu