Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity

Abstract

Gravity is a constitutive force that influences life on Earth. It is sensed and translated into biochemical stimuli through the so called “mechanosensors”, proteins able to change their molecular conformation in order to amplify external cues causing several intracellular responses. Mechanosensors are widely represented in the human body with important structures such as otholiths in hair cells of vestibular system and statoliths in plants. Moreover, they are also present in the bone, where mechanical cues can cause bone resorption or formation and in muscle in which mechanical stimuli can increase the sensibility for mechanical stretch. In this review, we discuss the role of mechanosensors in two different conditions: normogravity and microgravity, emphasizing their emerging role in microgravity. Microgravity is a singular condition in which many molecular changes occur, strictly connected with the modified gravity force and free fall of bodies. Here, we first summarize the most important mechanosensors involved in normogravity and microgravity. Subsequently, we propose muscle LIM protein (MLP) and sirtuins as new actors in mechanosensing and signaling transduction under microgravity.

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

“…It has been reported that astronauts, who experienced long-duration space missions in microgravity, lose bone mass and encountered fracture risk [ 120 , 121 ]. Mononuclear precursor cells cultured in the perfusion bioreactor system mimicking microgravity showed a severe increase of TRAP positive cells and expression level of osteoclast-specific genes [ 122 , 123 ]. Sambandam et al evaluated the involvement of autophagy in weightlessness-induced osteoclastogenesis and reported up-regulation of autophagy-associated molecules such as Trp53 (Transformation-related protein 53), Prkaa1 (Protein kinase AMP-activated catalytic subunit alpha 1), autophagosome components, and markers such as Atg5, 16L, 9b, and LC3.…”

Mechanotransduction in Prokaryotes: A Possible Mechanism of Spaceflight Adaptation

“…On a more complex level, the surfaces of many eukaryotic cells exhibit focal adhesion (FA) structures which physically link the extracellular matrix to the internal cytoskeleton through complexes of signaling proteins, among them mechanosensitive transmembrane proteins. Such structures establish both physical and functional connections between the cell and its external environment (reviewed in [ 19 , 20 ]).…”

“…Evidence is accumulating that LINC complexes allow for the rapid mechanotransduction of signals from the cytoplasmic membrane and cytoskeleton directly through the nuclear membrane to the nucleoskeleton, enabling rapid gene expression responses (reviewed in [ 17 ]). It is thought that the LINC complex is intimately involved in modulation of genome expression in response to mechanical stimuli through chromatin remodeling and recruitment of DNA and RNA polymerases, ligases, acetylases, methylases, and cyclin-dependent kinases, resulting in changes in gene expression at the transcriptional, translational, post-translational, and epigenetic levels [ 19 , 20 ]. The details of the myriad of eukaryotic mechanotransduction systems, though not yet completely elucidated, are currently being actively investigated [ 17 ].…”

Microgravity, Bone Homeostasis, and Insulin-like Growth Factor-1

“…Cell shape distortion involves cytoskeletal rearrangement of actin fibers and microtubules, both of which are known to be integral players in mechanotransduction. Osteocyte cilia, dendritic extensions, and integrins in the extracellular matrix also act as mechanosensors [4,5]. Hillsley and Frangos propose that the bone loss observed in disuse and microgravity is due to a lack or decreased interstitial fluid flow [6] Liu and associates have shown that osteocytes also respond to changes in hydraulic pressure.…”

“…Other structures within bone may also play a role in the response of bone to mechanical forces, including ion channels, connexins, integrins, and the glycocalyx [2,5].…”