Fig. 5.

Mechanical load controls the stability of costameric proteins. Both astronauts and volunteers undergoing bed rest experience decreased muscle strength (data derived with permission from Refs (5) and (9)). We hypothesize that unloading, both on Earth and during spaceflight, leads to alteration of lateral force transmission by decreasing the expression of specific proteins located at the costameres (represented as anchors in central panel, see measured expression values in Figs 2 and4; Figures S2, S4, Tables S7, and S9, Supplementary Material), which couple the contractile apparatus to the extracellular matrix. Under normal weight load at Earth gravity, costameres allow for efficient transmission of contractile force from the muscle fibers to the ECM, and they prevent muscle contraction from damaging the sarcolemma. As a consequence of unloading, the expression of specific costameric proteins, thus the transmission of lateral force may result inefficient. Our data also show that the downregulation of plakoglobin (JUP) and its specific interactors DSG1 and DSP is strong both in bed rest and spaceflight. Plakoglobin is part of a complex that stabilizes the insulin receptor (not quantified in this dataset) on the sarcolemma, so it will be of interest to further investigate its role in the development of insulin resistance during muscle inactivity on Earth and in space.