Calcium- and Integrin-binding Protein 1 Regulates Megakaryocyte Ploidy, Adhesion, and Migration

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2011 Dec 1

PMID 22128142

Citations 14

Authors

John C Kostyak

Meghna U Naik

Ulhas P Naik

Affiliations

Soon will be listed here.

Abstract

Megakaryocytes are large, polyploid cells that produce platelets. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further characterize the role of CIB1 in megakaryopoiesis, we used a Cib1(-/-) mouse model. Cib1(-/-) mice have more platelets and BM megakaryocytes than wild-type (WT) controls (P < .05). Furthermore, subsequent analysis of megakaryocyte-CFU production revealed an increase with Cib1 deletion compared with WT (P < .05). In addition, BM from Cib1(-/-) mice, cultured with thrombopoietin (TPO) for 24 hours, produced more highly polyploid megakaryocytes than WT BM (P < .05). Subsequent analysis of TPO signaling revealed enhanced Akt and ERK1/2 phosphorylation, whereas FAK(Y925) phosphorylation was reduced in Cib1(-/-) megakaryocytes treated with TPO. Conversely, platelet recovery in Cib1(-/-) mice after platelet depletion was attenuated compared with WT (P < .05). This could be the result of impaired adhesion and migration, as adhesion to fibrinogen and fibronectin and migration toward an SDF-1α gradient were reduced in Cib1(-/-) megakaryocytes compared with WT (P < .05). In addition, Cib1(-/-) megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in megakaryopoiesis, initially by negatively regulating TPO signaling and later by augmenting proplatelet production.

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References

Naik M, Naik U . Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Blood. 2003; 102(10):3629-36. DOI: 10.1182/blood-2003-05-1703. View

Larson M, Watson S . Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3. Blood. 2006; 108(5):1509-14. DOI: 10.1182/blood-2005-11-011957. View

Zayed M, Yuan W, Leisner T, Chalothorn D, McFadden A, Schaller M . CIB1 regulates endothelial cells and ischemia-induced pathological and adaptive angiogenesis. Circ Res. 2007; 101(11):1185-93. DOI: 10.1161/CIRCRESAHA.107.157586. View

Hu Z, Slayton W, Rimsza L, Bailey M, Sallmon H, Sola-Visner M . Differences between newborn and adult mice in their response to immune thrombocytopenia. Neonatology. 2010; 98(1):100-8. PMC: 2914362. DOI: 10.1159/000280413. View

Tortolani P, Johnston J, Bacon C, McVicar D, Shimosaka A, Linnekin D . Thrombopoietin induces tyrosine phosphorylation and activation of the Janus kinase, JAK2. Blood. 1995; 85(12):3444-51. View

Mazharian A, Watson S, Severin S . Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol. 2009; 37(10):1238-1249.e5. PMC: 2755112. DOI: 10.1016/j.exphem.2009.07.006. View

Naik M, Naik U . Contra-regulation of calcium- and integrin-binding protein 1-induced cell migration on fibronectin by PAK1 and MAP kinase signaling. J Cell Biochem. 2011; 112(11):3289-99. PMC: 3196778. DOI: 10.1002/jcb.23255. View

de Sauvage F, Hass P, Spencer S, Malloy B, Gurney A, Spencer S . Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature. 1994; 369(6481):533-8. DOI: 10.1038/369533a0. View

Naik U, Naik M . Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003; 102(4):1355-62. DOI: 10.1182/blood-2003-02-0591. View

10.

Naik M, Pham N, Beebe K, Dai W, Naik U . Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells. Int J Cancer. 2010; 128(3):587-96. PMC: 2954264. DOI: 10.1002/ijc.25388. View

11.

Mazharian A, Thomas S, Dhanjal T, Buckley C, Watson S . Critical role of Src-Syk-PLC{gamma}2 signaling in megakaryocyte migration and thrombopoiesis. Blood. 2010; 116(5):793-800. DOI: 10.1182/blood-2010-03-275990. View

12.

Kauselmann G, Weiler M, Wulff P, Jessberger S, Konietzko U, Scafidi J . The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically with synaptic plasticity. EMBO J. 1999; 18(20):5528-39. PMC: 1171621. DOI: 10.1093/emboj/18.20.5528. View

13.

Fuhrken P, Apostolidis P, Lindsey S, Miller W, Papoutsakis E . Tumor suppressor protein p53 regulates megakaryocytic polyploidization and apoptosis. J Biol Chem. 2008; 283(23):15589-600. PMC: 2414295. DOI: 10.1074/jbc.M801923200. View

14.

Sieg D, Ilic D, Jones K, Damsky C, Hunter T, Schlaepfer D . Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK- cell migration. EMBO J. 1998; 17(20):5933-47. PMC: 1170921. DOI: 10.1093/emboj/17.20.5933. View

15.

Lee M, Kim Y, Lee S, Kim J, Kim S, Ye S . Integrin signaling and cell spreading mediated by phorbol 12-myristate 13-acetate treatment. J Cell Biochem. 2006; 99(1):88-95. DOI: 10.1002/jcb.20830. View

16.

Naik M, Nigam A, Manrai P, Millili P, Czymmek K, Sullivan M . CIB1 deficiency results in impaired thrombosis: the potential role of CIB1 in outside-in signaling through integrin alpha IIb beta 3. J Thromb Haemost. 2009; 7(11):1906-14. PMC: 7034629. DOI: 10.1111/j.1538-7836.2009.03581.x. View

17.

Lane W, Dias S, Hattori K, Heissig B, Choy M, Rabbany S . Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood. 2000; 96(13):4152-9. View

18.

Chanprasert S, Geddis A, Barroga C, Fox N, Kaushansky K . Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytes. Cell Signal. 2005; 18(8):1212-8. DOI: 10.1016/j.cellsig.2005.09.010. View

19.

Wang Q, Xie S, Chen J, Fukasawa K, Naik U, Traganos F . Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol. 2002; 22(10):3450-9. PMC: 133784. DOI: 10.1128/MCB.22.10.3450-3459.2002. View

20.

Hitchcock I, Fox N, Prevost N, Sear K, Shattil S, Kaushansky K . Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout. Blood. 2007; 111(2):596-604. PMC: 2200856. DOI: 10.1182/blood-2007-05-089680. View