Beschreibung:
<jats:p>Cytoskeletal proteins are crucial in maintaining cellular structure and, in certain cell types, also play an essential role in motility and shape change. Nitric oxide (NO) is an important paracrine mediator of vascular and platelet function and is produced in the vasculature by the enzyme NO synthase type 3 (NOS-3). Here, we demonstrate in human platelets that the polymerization state of β-actin crucially regulates the activation state of NOS-3, and hence NO formation, through altering its binding of heat shock protein 90 (Hsp90). We found that NOS-3 binds to the globular, but not the filamentous, form of β-actin, and the affinity of NOS-3 for globular β-actin is, in turn, increased by Hsp90. Formation of this ternary complex among NOS-3, globular β-actin, and Hsp90, in turn, results in an increase in both NOS activity and cyclic guanosine-3′,5′-monophosphate, an index of bioactive NO, as well as an increased rate of Hsp90 degradation, thus limiting the duration for which NOS-3 remains activated. These observations suggest that β-actin plays a critical role in regulating NO formation and signaling in platelets.</jats:p>