English

Andrei Garzon Dasgupta

STIM1-ORAI1 direct interaction cannot govern store-operated calcium entry (SOCE) in platelets

Store-operated calcium entry (SOCE) plays an important role in platelet function. It is generally assumed that the mechanism of SOCE relies on the direct interaction of STIM1 and ORAI1 proteins with specific STIM1:ORAI1 stoichiometry. However, in platelets, other pathways may take place. Here we aim to investigate the mechanisms of SOCE in platelets. We developed a lattice-based mathematical model that represented STIM1-ORAI1 interactions and applied it to both HEK cells, where SOCE mechanism is well established, and platelets. The model was able to describe STIM1-ORAI1 behavior in HEK cells successfully. We used the same parameters for protein interaction and applied them to platelets. As a result, we demonstrated that the number of STIM1 proteins on ER membrane could not assure the needed stoichiometry to proper SOCE in platelets.

(A) STIM1-ORAI1 interaction for HEK cells. Bound proteins are presented by brown, STIM1 in cluster – green, free proteins - red. (B) STIM1-ORAI1 puncta formation dependance on clustering probability. Dashed lines represent same process for D=0.01 〖μm〗^2/s (C) Typical system state at t=100ms for different clustering probabilities
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#platelets#mathematical modeling#store-operated calcium entry#platelet intracellular signaling