Fig. 9. A model summarizing a proposed myosin folding pathway in striated muscle cells. The molecular chaperones in Step 1 interact with nascent and partially folded myosin molecules. The light chains are not depicted in this drawing but are assumed to associate with the light chain binding region of the myosin head soon after synthesis (Srikakulam and Winkelmann, 1999). This first step involves the initial folding and dimerization of the myosin molecule. Step 2 involves the formation of the myosin maturation complexes containing partially folded myosin and the molecular chaperones Hsc70 and Hsp90. Myosin transit through this intermediate is normally rapid. However, these intermediates accumulate if myofibril assembly is delayed or if Hsp90 activity is inhibited with geldanamycin (GA). Myosin filaments emerge from the maturation complexes containing folded native myosin and are then incorporated into nascent myofibrils in the final step (3) of the pathway.