Proteostasis of heat shock protein 90 in skeletal muscles of the long-tailed ground squirrel during hibernation

Abstract

We investigated changes in the content of heat shock protein 90 in m. soleus (comprised of mainly fibers expressing the MyHC slow isoform I) and m. gastrocnemius (composed of mainly fibers expressing the MyHC fast isoforms II) of the long-tailed ground squirrel Urocitellus undulatus in different periods of the annual cycle: summer activity (seasonal control), hypothermia/torpor, winter (interbout) activity. The content of the protein in both muscles was found not to change throughout the entire hibernation period despite the development of atrophic changes, more pronounced in fast m. gastrocnemius. The role of HSP90 in maintaining the stability of giant sarcomeric titin protein molecules is discussed with reference to animal's entry into and exit from hypothermia, when the activity of calpain proteases increases due to the increased content of Ca2+ in the cytosol of muscle cells; and with respect to the torpor, when the activity of calpains is, most likely, not inhibited completely. During the interbout activity with an observed increased titin turnover in squirrel's striated muscles, a constant content of HSP90 appears to be required for the correct folding of newly synthesized titin molecules and their integration into sarcomeres, as well as for the removal of misfolded titin molecules and other proteins. Thus, HSP90 proteostasis in skeletal muscles of the long-tailed ground squirrel can contribute to maintaining a steady-state level of titin and, possibly, other sarcomeric proteins during hibernation, which, in turn, will contribute to maintaining a highly ordered sarcomeric structure and the necessary level of muscle contractile activity in different phases of the torpor-arousal cycle.