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Title: The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function.
Authors: Lau, Lai-Man;Wee, Janet L;Wright, Mark D;Moseley, Gregory W;Hogarth, P Mark;Ashman, Leonie K;Jackson, Denise E
Affiliation: Kronheimer Building, Austin Research Institute, Austin Hospital, Studley Rd, Heidelberg, Victoria 3084 Australia.
Issue Date: 29-Jun-2004
Citation: Blood 2004; 104(8): 2368-75
Abstract: 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.
Internal ID Number: 15226180
DOI: 10.1182/blood-2003-12-4430
Type: Journal Article
Subjects: Animals
Antigens, CD.genetics.metabolism
Antigens, CD151
Blood Platelets.cytology.metabolism.secretion
Cell Adhesion
Mice, Knockout
Platelet Aggregation.genetics
Platelet Glycoprotein GPIIb-IIIa Complex.metabolism
Protein Binding
Secretory Vesicles.metabolism
Signal Transduction
Appears in Collections:Journal articles

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