Please use this identifier to cite or link to this item:
Title: The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function.
Austin 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
Publication information: 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.
Gov't Doc #: 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

Files in This Item:
File Description SizeFormat 
15226180.pdf383.04 kBAdobe PDFThumbnail
Show full item record

Page view(s)

checked on Dec 2, 2022


checked on Dec 2, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.