| First Author | Lau LM | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 8 | Pages | 2368-75 |
| PubMed ID | 15226180 | Mgi Jnum | J:93758 |
| Mgi Id | MGI:3505654 | Doi | 10.1182/blood-2003-12-4430 |
| Citation | Lau LM, et al. (2004) The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function. Blood 104(8):2368-75 |
| abstractText | The tetraspanin family member CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD151 in murine platelets. Immunoprecipitation/Western blot studies reveal a constitutive physical association of CD151 with integrin alpha(IIb)beta(3) complex under strong detergent conditions. Using CD151-deficient mice, we show that the platelets have impaired 'outside-in' integrin alpha(IIb)beta(3) signaling with defective platelet aggregation responses to protease-activated receptor 4 (PAR-4) agonist peptide, collagen, and adenosine diphosphate (ADP); impaired platelet spreading on fibrinogen; and delayed kinetics of clot retraction in vitro. This functional integrin alpha(IIb)beta(3) defect could not be attributed to altered expression of integrin alpha(IIb)beta(3). CD151(-/-) platelets displayed normal platelet alpha granule secretion, dense granule secretion, and static platelet adhesion. In addition, CD151(-/-) platelets displayed normal 'inside-out' integrin alpha(IIb)beta(3) signaling properties as demonstrated by normal agonist-induced binding of soluble fluorescein isothiocyanate (FITC)-fibrinogen, JON/A antibody binding, and increases in cytosolic-free calcium and inositol 1,4,5 triphosphate (IP(3)) levels. This study provides the first direct evidence that CD151 is essential for normal platelet function and that disruption of CD151 induced a moderate outside-in integrin alpha(IIb)beta(3) signaling defect. |
