Targeting GSK3 to attenuate spaceflight-induced SERCA dysfunction: Lessons from hindlimb-suspended mice

• In the absence of gravity, muscles become unloaded, reducing their size, strength, and endurance. • Calcium (Ca 2+ ) dysregulation due to impairments in sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) function may be one reason for the decline in muscle performance. • Our previous work has shown that genetic reduction of glycogen synthase kinase 3 (GSK3) maintains soleus muscle mass and strength in mice after 7 days of hindlimb suspension. • Here, we tested whether these benefits could be, in part, due to an improvement in SERCA activity. • We show that muscle-specific GSK3 knockdown enhances soleus maximal SERCA activity, SERCA1 protein content, soleus relaxation and soleus muscle endurance.