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Effect of Microgravity on Signal Transduction Pathways in Cell Cytoskeleton

BY: Shivani Sharma | Category: Others | Submitted: 2012-12-07 10:20:48
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Article Summary: "Many of the investigators have reported and demonstrated in their results that this complex network of fibers is sensitive to quite a few environmental factors such as microgravity and altered gravitational forces [49].The cytoskeleton is basically a complex network of fibres that is found to be sensitive to environmental factor.."


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The cytoskeleton is a cellular skeleton contained within a cell's cytoplasm and it is abbreviated as CSK. It is present in all cells and has structures like cilia, flagella, lamellipodia. It has a function in intracellular transport and cellular division. The cytoskeleton has a role in providing a cell its shape. It also generates the forces required for cell motility. Structure-wise, it is basically an internal network of at least three types of cytosolic fibers. They are actin filaments, microtubules and intermediate filaments. Actin is one of the most highly conserved and abundant eukaryotic proteins. It is simultaneously polymerized and depolymerized within the cells to produce and assist the processes of cellular motility, tissue formation and repair.

It has been reported by several scientists on the basis of their conducted researches that microgravity effects the cytoskeleton structure and its function, which in turn influences motility of cells, esp. T-cells. Morphological differences have been observed in both the actin and microtubules of the cytoskeleton in simulated microgravity. Gruener and Hughes-Fulford reported that actin reorganization responded to the changes in gravity level and showed unusual assembly of actin stress fibers during spaceflight. Also, cancer cells grown under microgravity's influence exhibited alterations in microtubule filaments.

The cytoskeleton is regulated by many signal transduction pathway. The Basic pathway is as follows:
1. A starting initial signal for neutrophils for their migration to the site of inflammation is provided by cytokines such as fMLP.
2. It binds and activates a class of G-protein coupled receptors (Ligand binding). This results into the activation of two pathways:
2.1. PLC- gamma is activated and it leads to generation of inositol-1, 4, 5-phosphate (IP3) and diacylglycerol (DAG), which results in DAG-mediated activation of PKC and release of intracellular stored calcium in ER (Endoplasmic reticulum).
2.2. Adenylyl cyclase also gets activated leading to an elevation in the level of cytosolic cAMP resulting into activation of SERCA pump.
Thus, stimulation of neutrophils with pro-inflammatory cytokines e.g. fMLP (in this case) activates a signal transduction pathway resulting into an increase in the level of cytosolic calcium and this intra-cellular stored calcium has been found to be essential for the development of actin based migration.

Migration of cells in the body is a key point to be discussed. Each cell, with special focus on T-cells and other immune cells, need to travel to their respective sites in order to serve their function. The immune cells require to migrate to the sites of infection/ inflammation to play a role in defending the body against microbes. As the studies have revealed that this migration of cell is strongly dependent upon the cytoskeleton which is then found to be effected by microgravity.

The structure of cells is found to be altered in microgravity with differences in the cytoskeleton, apoptosis rate and also, the cellular responses to the environment (Sakar et al., 1999; Uva et al.,2002; Sundareasan et al.,2001). Cytoskeletal components such as microtubules are found to be changed in microgravity. Even adter the knowledge of the altered cell morphology and functions observed in several experiments performed in microgravity, it is found that the embryos of some animal species can still develop into living organisms that are able to carry out the function of reproduction. Although, the microgravity-induced pathology of embryo development has not been clearly explained yet in mammals nor in humans, nor is it fully understood. Findings of the research works on the pathology of development in altered gravity have often been quite contradictory. In order to explain the cellular mechanisms that are involved in the malformations of embryos that might be induced in microgravity, there are many more studies of cell development during embryogenesis that need to be carried out. One may need to look further to the fields of teratology and developmental pathology, to examine cellular processes in embryonic development in microgravity with the precise yet defined aim of defining and standardizing the abnormal data obtained during such studies. Embryonic processes such as cell sorting, intercalation and embryonic waves need to be taken under deep and wide study in microgravity to see what changes have occurred and why. Studies in artificially produced microgravity in clinostats should be compared with the studies of microgravity of space and then, the studies of artificially produced 1G in space should be compared to the studies of 1G earth normal gravity controls [Effect of microgravity on cell cytoskeleton and embryogenesis, Susan J crowford-Young*, Int. J. Dev. Biol. 50: 183-191 (2006)].

Many of the investigators have reported and demonstrated in their results that this complex network of fibers is sensitive to quite a few environmental factors such as microgravity and altered gravitational forces [49].The cytoskeleton is basically a complex network of fibres that is found to be sensitive to environmental factors including microgravity and altered gravitational forces. Cytoskeletal integrity plays a key role in cellular functions such as transport of cell organelles; regulation of cytoskeletal activity plays a role in cell maintenance and also regulates cell division and apoptosis. Cytoskeletal and mitochondria alterations in cultured human lymphocyte (Jurkat) cells slightly after exposure to spaceflight and in insect cells of Drosophila melanogaster (Schneider S-1) after exposure to conditions that were created by clinostat rotation has been experimented. Jurkat cells were taken out on the space shuttle in Biorack cassettes while on the other hand, Schneider S-1 cells were exposed to altered gravity forces as produced by clinostat rotation. The effects of both treatments were found to be similar in the different cell types. Fifty percent of cells showed effects on the microtubule network in both cell lines. After 4 and 48 hours of culture, under these experimental conditions mitochondria clustering and morphological alterations of mitochondrial cristae was observed to a variety of degrees and analysed thereafter. Jurkat cells were seen to undergo cell divisions during the exposure to spaceflight, though a large number of apoptotic cells was also observed. Quite similar results were obtained in Schneider S-1 cells that were cultured under clinostat rotation. Both cell lines had displayed mitochondria abnormalities and mitochondria clustering toward one side of the cells which is considered to be the result of microtubule disruption and also due to the failure of mitochondria transport along microtubules. The number of mitochondria was found to be increased in cells exposed to altered gravity while cristae morphology was found to be severely affected indicating altered mitochondria function. These results have shown that both spaceflight as well as altered gravity produced by clinostat rotation greatly affects microtubule and mitochondria organization and therefore results in increases in apoptosis. [Grant numbers: NAG 10-0224, NAG2-985].

Therefore, it can be concluded that in one way or other, the molecular structure of life on earth require gravity for survival and the absence of gravity influences the basic mechanisms of signal transduction essential to the cytoskeleton structure to a large extent which is essential to give a cell its shape and size and help maintain its motility. It has been clearly postulated now that the gravity has a deep effect on the biological systems and so its importance can't be neglected. The astronauts traveling to Moon and mars have shown significant changes in their body systems and hence, by studying the effects of gravity on life on earth, we would be able to design and propound therapeutic and preventive measures.

About Author / Additional Info:
A Budding biotechnologist + writer from India.. Visit http://in.linkedin.com/pub/shivani-sharma/4b/91b/384 or refer cv.napping@gmail.com for more details.
Researcher ID- J-4200-2012

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