Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration

Blood. 2012 Jan 19;119(3):838-46. doi: 10.1182/blood-2011-04-346098. Epub 2011 Nov 29.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • Blotting, Western
  • Calcium / pharmacology*
  • Calcium-Binding Proteins / physiology*
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Chemokine CXCL12 / metabolism
  • Megakaryocytes / cytology
  • Megakaryocytes / physiology*
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Ploidies*
  • Protein Binding
  • Signal Transduction
  • Thrombopoiesis
  • Thrombopoietin / metabolism


  • Calcium-Binding Proteins
  • Chemokine CXCL12
  • Cib1 protein, mouse
  • Thrombopoietin
  • Calcium