title: Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration.
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.
authors: Department of Biological Sciences, University of Delaware, Newark, USA.
authors: John C
authors: JC
authors: Kostyak
authors: Meghna U
authors: MU
authors: Naik
authors: Ulhas P
authors: UP
authors: Naik
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011003:Ploidies; D011485:Protein Binding; D015398:Signal Transduction; D034061:Thrombopoiesis; D013926:Thrombopoietin / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D054377:Chemokine CXCL12; C491605:Cib1 protein, mouse; D013926:Thrombopoietin; D002118:Calcium