FIGURE 7.

Proposed model for the role of HSP90 in the eNOS activation cycle. A, in resting cells, eNOS is associated in an inactive form to caveolin-1. B, following a rise in intracellular [Ca²⁺], interaction of eNOS with Ca²⁺-CAM and with HSP90 promotes the dissociation of the synthase from caveolin-1 and its activation in the cytosol. The reversibility of this process is assured by the formation of a HSP90-eNOS-calpain heterocomplex resistant to proteolysis. C, in the absence of active HSP90, the complex formation does not occur, and eNOS becomes highly susceptible to degradation by active calpain.