RhoGTPases as Key Players in Mammalian Cell Adaptation to Microgravity

Figure 5

Proposed models describing the regulations of RhoA and Rac1 activities in space-related conditions. On Earth MSCs are well spread and exhibit a tensed cytoskeleton in particular of microtubules, intermediate filaments, and actin stress fibers associated with stable focal adhesions within the extracellular matrix. These elements are controlled by GTPases RhoA and Rac1. We hypothesize that during short-term exposure to microgravity, RhoA might be inhibited to allow cytoskeleton reorganization in respect to the new mechanical status. Cell tension reduction might be mandatory during this adaptation. At the same time, Rac1 is activated to control peripheral actin polymerization and induces ROS production. All these events lead rapidly to a rounder cell shape with disorganization of microtubules, stress fibers, intermediate filaments, and focal adhesions. Transcription may be also altered as nucleus shape is changed. In these conditions, cell is still able to migrate. When exposure to microgravity is prolonged both RhoA and Rac1 might be inhibited explaining decreases in osteogenesis and myogenesis and enhancement of adipogenesis of MSCs. In addition, RhoA inhibition limits fibrillogenesis (a tension-dependent process); extracellular matrix is not properly synthesized and lost its mechanical properties appearing softer for MSCs, reinforcing adipogenesis. At that time, migration is inhibited, consistent with cytoskeleton alterations and Rac1 decrease. MSCs become very round, have low adhesion, and may initiate anoikis.

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