Thrombin induces the association of cyclic ADP-ribose-synthesizing CD38 with the platelet cytoskeleton.
The effect of platelet stimulation on the subcellular localization of CD38, a membrane glycoprotein that catalyses the synthesis of cyclic ADP-ribose from beta-NAD+ was investigated. Treatment of human platelets with thrombin caused the association of about 40% of the total ADP-ribosyl cyclase activity with the cytoskeleton, through the translocation of the CD38 molecule from the Triton X-100-soluble to the insoluble fraction. The interaction of CD38 with the cytoskeleton was a specific and reversible process, mediated by the binding to the actin-rich filaments and was inhibited by treatment of platelets with cytochalasin D. This event was regulated by integrin alphaIIb beta3 and platelet aggregation as it was prevented by the inhibition of fibrinogen binding and was not observed in platelets from a patient affected by Glanzmann thrombasthenia. These results demonstrate that the subcellular localization of CD38 can be influenced by platelet stimulation with physiological agonists, and that membrane CD38 can interact with intracellular proteins.
Torti
M
M
Department of Biochemistry, University of Pavia, Italy.
Festetics
E T
ET
Bertoni
A
A
Sinigaglia
F
F
Balduini
C
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000199:Actins / Q000097:blood; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D015703:Antigens, CD / Q000097:blood / Q000187:drug effects; D000943:Antigens, Differentiation / Q000097:blood* / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D036563:Cyclic ADP-Ribose; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes / Q000097:blood / Q000187:drug effects; D009244:NAD+ Nucleosidase / Q000097:blood* / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011485:Protein Binding; D013917:Thrombin / Q000494:pharmacology*
D000199:Actins; D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D009842:Oligopeptides; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D013917:Thrombin