Cytoskeleton‐dependent inhibition of the ADP‐ribosyl cyclase activity of CD38 in thrombin‐stimulated platelets

FEBS Letters

Torti, Mauro²  Bertoni, Alessandra²  Tolnai Festetics, Enrico²  Balduini, Cesare²  Sinigaglia, Fabiola¹ 

[1] Institute of Biological Chemistry, University of Genoa, viale Benedetto XV 1, 16132 Genoa, Italy;Department of Biochemistry, University of Pavia, via Bassi 21, 27100 Pavia, Italy

关键词: ADP-ribosyl cyclase;    CD38;    Cytoskeleton;    Platelet;    Ca2+ mobilization;    NGD+;    nicotinamide guanine dinucleotide;    cGDPR;    cyclic GDP-ribose;    cADPR;    cyclic ADP-ribose;    ADPR;    ADP-ribose;    IP3;    inositol 1;    4;    5-trisphosphate;   

DOI  :  10.1016/S0014-5793(98)00712-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Stimulation of human platelets with thrombin caused a 42% inhibition of the ADP-ribosyl cyclase activity of membrane CD38. This effect was mediated by the activation of the platelet thrombin receptor rather than by proteolysis of CD38, and was not due to a different distribution of the synthesised nucleotide or to a reduced accessibility of CD38 to the substrate. The inhibitory effect of thrombin required actin polymerisation and was not observed when interaction of CD38 with the cytoskeleton was prevented by cytochalasin D. Finally, we analysed whether cADPR could play a role as a Ca²⁺-mobilising agent in human platelets. Using saponin-permeabilised cells, we found that unlike IP₃, cADPR did not induce any release of Ca²⁺ from intracellular stores. These results indicate that the enzymatic activity of membrane CD38 can be modulated by platelet activation, and that the function of this glycoprotein is probably not related to Ca²⁺ mobilisation.

【 授权许可】

Unknown