RhoGTPases as Key Players in Mammalian Cell Adaptation to Microgravity

Louis, Fiona; Deroanne, Christophe; Nusgens, Betty; Vico, Laurence; Guignandon, Alain

doi:10.1155/2015/747693

Cited by 35 publications

(33 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rho, Cdc42 and Rac are recognized as the most important regulators of actin assembly (Lee and Dominguez 2010). During SMG, the reorganization of actin cytoskeleton may be attributed to Rho, which is reported to act as a sensor for microgravity (Louis et al 2015). To clarify the mechanism of SMG remodeling F-actin, we utilized Y-27632, an inhibitor of Rock (a downstream factor of Rho), and found that Y-27632 significantly reversed the reorganization of F-actin induced by SMG.…”

Section: Discussionmentioning

confidence: 99%

“…Rock phosphorylates LIM kinase, which then phosphorylates confilin, resulting in actin cytoskeleton stabilization (Nakashima and Lazo 2010). It has been reported that Rho-GTPases act as key sensors in cell adaptation to microgravity and mediates the reorganization of actin cytoskeleton under microgravity (Louis et al 2015). But the role of Rho signaling in cell migration under microgravity is still unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness

et al. 2016

View full text Add to dashboard Cite

Exposure to microgravity during space flight affects almost all human physiological systems. Migration, proliferation, and differentiation of stem cells are crucial for tissues repair and regeneration. However, the effect of microgravity on the migration potentials of bone marrow mesenchymal stem cells (BMSCs) is unclear, which are important progenitor and supporting cells. Here, we utilized a clinostat to model simulated microgravity (SMG) and found that SMG obviously inhibited migration of rat BMSCs. We detected significant reorganization of F-actin filaments and increased Young's modulus of BMSCs after exposure to SMG. Moreover, Y-27632 (a specific inhibitor of ROCK) abrogated the inhibited migration capacity and polymerized F-actin filament of BMSCs under SMG. Interestingly, we found that transferring BMSCs to normal gravity also attenuated the polymerized F-actin filament and Young's modulus of BMSCs induced by SMG, but could not recover migration capacity of BMSCs inhibited by SMG. Taken together, we propose that SMG inhibits migration of BMSCs through remodeling F-actin and increasing cell stiffness.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Therefore, they seem to be at the forefront in cell adaptation to microgravity. According to Louis et al (186), on 1 × g , cell tension is sensed through the cytoskeleton via microtubules, intermediate filaments, and actin stress fibers associated with focal adhesions within the extracellular matrix. These elements are controlled by GTPases RhoA and Rac1.…”

Section: Cytoskeletonmentioning

confidence: 99%

Mechanotransduction as an Adaptation to Gravity

Najrana

Sanchez‐Esteban

2016

Front. Pediatr.

View full text Add to dashboard Cite

Gravity has played a critical role in the development of terrestrial life. A key event in evolution has been the development of mechanisms to sense and transduce gravitational force into biological signals. The objective of this manuscript is to review how living organisms on Earth use mechanotransduction as an adaptation to gravity. Certain cells have evolved specialized structures, such as otoliths in hair cells of the inner ear and statoliths in plants, to respond directly to the force of gravity. By conducting studies in the reduced gravity of spaceflight (microgravity) or simulating microgravity in the laboratory, we have gained insights into how gravity might have changed life on Earth. We review how microgravity affects prokaryotic and eukaryotic cells at the cellular and molecular levels. Genomic studies in yeast have identified changes in genes involved in budding, cell polarity, and cell separation regulated by Ras, PI3K, and TOR signaling pathways. Moreover, transcriptomic analysis of late pregnant rats have revealed that microgravity affects genes that regulate circadian clocks, activate mechanotransduction pathways, and induce changes in immune response, metabolism, and cells proliferation. Importantly, these studies identified genes that modify chromatin structure and methylation, suggesting that long-term adaptation to gravity may be mediated by epigenetic modifications. Given that gravity represents a modification in mechanical stresses encounter by the cells, the tensegrity model of cytoskeletal architecture provides an excellent paradigm to explain how changes in the balance of forces, which are transmitted across transmembrane receptors and cytoskeleton, can influence intracellular signaling pathways and gene expression.

show abstract

“…The previously described rapid reaction and adaptation of an oxidative burst reaction [ 32 ] suggests a direct effect on the NADPH oxidase, which is a membrane-bound multiprotein complex closely associated with cytoskeletal dynamics [ 58 , 59 ] and mechanosensitivity [ 3 ]. Also, RhoGTPases are potential candidates to explain the structural cellular changes in microgravity [ 60 ]. In our study, we detected a significant up-regulation of p22 phox after 20 s and of p47 phox after 5 min of microgravity, whereas rac-1 was down-regulated after 5 min of microgravity.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity

Tauber

Christoffel

Thiel

et al. 2018

IJMS

View full text Add to dashboard Cite

Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, we investigated the immediate effect of altered gravity on the transcription of 86 genes involved in reactive oxygen species metabolism, antioxidative systems, and cellular response to oxidative stress, using parabolic flight and suborbital ballistic rocket experiments and microarray analysis. In human myelomonocytic U937 cells, we detected a rapid response of 19.8% of all of the investigated oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted after 5 min of microgravity. After the almost complete adaptation of initially altered transcripts, a significant second pool of differentially expressed transcripts appeared. In contrast, we detected nearly no response of oxidative stress-related transcripts in human Jurkat T cells to altered gravity. In conclusion, we assume a very well-regulated homeostasis and transcriptional stability of oxidative stress-related pathways in altered gravity in cells of the human immune system.

show abstract

RhoGTPases as Key Players in Mammalian Cell Adaptation to Microgravity

Cited by 35 publications

References 149 publications

Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness

Simulated microgravity inhibits the migration of mesenchymal stem cells by remodeling actin cytoskeleton and increasing cell stiffness

Mechanotransduction as an Adaptation to Gravity

Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity

Contact Info

Product

Resources

About