Distinct roles of ligand affinity and cytoskeletal anchorage in alphaIIbbeta3 (GP IIb/IIIa)-mediated cell aggregation and adhesion.
Platelet integrin alphaIIbbeta3 (GP IIb/IIla) is functionally modulated by changes in ligand affinity or in cytoskeletal anchorage. CHO cells transfected with wild-type/mutated alphaIIbbeta3 allow the dissection of the relative contributions of the two regulatory mechanisms in alphaIIbbeta3-mediated adhesion and aggregation. Mutations included a truncation of the cytoplasmic domain of the beta-subunit, resulting in a loss of cytoskeletal anchorage of alphaIIbbeta3, and a VGFFK-deletion of the alpha-subunit, resulting in a permanent high affinity state. alphaIIbbeta3-mediated cell aggregation is dependent on the high affinity state but only partially on the cytoskeletal anchorage of alphaIIbbeta3. In contrast, alphaIIbbeta3-mediated cell adhesion is dependent on the cytoskeletal anchorage but only partially on the high affinity state of alphaIIbbeta3. Thus, the functional evaluation of mutated alphaIIbbeta3 implies a differential role of affinity state and cytoskeletal anchorage for alphaIIbbeta3-mediated cell adhesion and aggregation.
Peter
Karlheinz
K
Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany. peterkh@medizin.ukl.uni-freiburg.de
Ahrens
Ingo
I
Schwarz
Meike
M
Bode
Christoph
C
Ylänne
Jari
J
D000818:Animals; D016466:CHO Cells; D002449:Cell Aggregation / Q000235:genetics / Q000502:physiology; D006224:Cricetinae; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010974:Platelet Aggregation / Q000235:genetics* / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics* / Q000502:physiology
D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex