Cellular+Motility+and+the+Elements+of+the+Cytoskeleton

==The cytoskeleton carries out three functions. It spatially organizes the contents of the cell, connects the cell physically and biochemically to the external environment, and it generates coordinated forces that allow the cell to move and change shape. In order to do this the cell assembles the cellular cytoskeleton that performs all of the previously mentioned functions. The cytoskeleton accomplishes this by integrating the activity of many cytoplasmic proteins and organelles. The structure is not fixed, but it is in fact a dynamic and adaptive structure which has component polymers and regulatory proteins that are in a constant state of change (flux). More than150 proteins have been found to contain binding domains for the protein actin, which polymerizes to form one of the key cytoskeletal filaments in cells. There are three main structures to the cytoskeleton, the microtubules, intermediate filaments and actin filaments. Microtubules are the thickest structure in the cytoskeleton and the stiffest. This structure is what aids in DNA segregation as the mitotic spindle during mitosis. The intermediate filaments Are the least stiff of the three polymers and resist tensile forces much more effectively than compressive forces. They can be cross-linked to each other by proteins called plectins (so can actin filaments and microtubules). They are not polarized and cannot support directional movement of molecular motors. Actin filaments are much less rigid than microtubules, but the high presence of crosslinkers that bind to actin filaments promote the assembly of highly organized, stiff structures. These filaments compose the leading edge of most motile cells and generate the forces involved in changes in cell shape like those that occur during phagocytosis. ==

(Picture taken from the University of Illinois at Chicago website)
==B. The purpose of the cytoskeleton is to give the cell a structure in order to keep the cytoplasmic area open and allow cellular processes to take place. It is also present to provide pathways for organelles and other cellular components to travel around the cell and be moved to where they are needed. It also allows for cellular movement which is necessary for single celled organisms so that they may move in order to survive. The cytoskeletal structure is also necessary in cells like nerve cells where new neural connections are being made between dendrites and other nerve cells. By understanding this movement and function within the cell, it can provide further insight in how to treat cells during research projects. In that way you may put cells in their most natural state when performing an experiment rather than leaving them on a hard petri dish that does not resemble their natural environment. Also, understanding how the cytoskeleton works within dangerous tissues like cancerous cells, different methods could be used during research in order to understand the differences and complexities of these cells and differences may lead to new solutions to destroy them. == ==C. One disease that is associated with the cytoskeleton is muscular dystrophy. Dystrophin became the first disease-related human gene to be identified by positional cloning in 1987. Dystrophin is an important part of the membrane attached cytoskeleton of muscle fibers. Mutations in the dystrophin gene causes Duchenne and Becker muscular dystrophy. One group of proteins known as the dystrophin-associated protein complex (DAPC) is believed to provide a molecular link between the actin cytoskeleton and the extracellular matrix in muscle cells, thereby sustaining sarcolemmal integrity during muscle contraction. == ==D. During the Second World War, in Szeged, Hungary, Albert Szent-Györgyi and colleagues discovered that the myosin originally described by Wilhelm Kühne in 1864 consisted of two proteins. In 1953 Michael Abercrombie set up some of the first time-lapse experiments with chicken fibroblasts and a phase-contrast microscope, he described the cell-motility cycle, which is the basis of our current understanding of how cells migrate. In 1960 Paul A. Weiss encouraged scientists and thinkers to think of the cell as an integrated whole, rather than a fluid filled sack with organelles. In 1972 Thomas Schroeder observed that the contractile ring (in sear urchin eggs) was composed of microfilaments that were similar to muscle actin filaments. In 1991 a study from Fuchs and colleagues identified a function for keratin filaments, which constitute a class of intermediate filaments that form networks in epithelial cells. In 1976, Afzelius described a disease that was caused by ciliary motility defects. He identified four patients who suffered from chronic bronchitis and sinusitis, and found that they produced live but immotile spermatozoa. It was noticed that the cilia from the cells of these patients lacked the motor protein dynein arms, which facilitate flagellar beating. == ==E. The paper "Diverse protective roles of the actin cytoskeleton during oxidative stress" reveals how actin oxidation that occurs in the erythrocytes of sickle cell patients may be the direct cause of the lack of morphological plasticity observed in irreversibly sickled red blood cells (ISCs). Since actin oxidation is known to result in changes in cytoskeleton organization and dynamics the following research has looked into how during episodes of crisis, ISCs accumulate C284-C373 intramolecularly disulfide bonded actin, which reduces actin filament dynamics. The results of this paper show that actin's C285 and C374 may help to protect the cell from oxidative stress arising from normal oxidative metabolism and contribute to the cell's general adaptive response to oxidative stress in the cytoskeleton. This gives us a greater understanding of the process because this shows us how different parts of the cytoskeleton react to different events and stressors in different way. The article "Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity,” describes the Rho-kinases role in the cytoskeleton. This review paper explains how the Rho-kinase has pleiotropic functions like the regulation of cellular contraction, motility, morphology, polarity, cell division and gene expression. Different members of the Rho family such as Rho, Rac, and Cdc42, regulate cytoskeletal reorganization in different ways. This paper is important since it organizes all of the understood functions of the Rho-kinases and how they affect the cell. This information can be used and applied to further studies. It also can give researches an idea of what other genes and proteins to look for when it comes to the functioning of the cytoskeleton. This paper gives important information on Cell contraction, actin organization, cell migration and neurite elongation and neuronal architecture, cytokinesis and other functions. Lastly, the article "The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53,” describes how influencing the cytoskeleton of cancer cells can lead to the death of cancerous cells. In certain cancer cell lines, depleting the microtubule-destabilizing protein stathmin/oncoprotein18 leads to a G2 cell cycle delay and apoptosis. It is found that the greater microtubule stability due to stathmin depletion extends the G2 phase in conjunction with low levels of p53. The importance of the results of this paper give us more information on what strengthens certain elements of the cytoskeleton and how they impact cellular processes, like mitosis. This is important when it comes to understanding apoptosis and other cell regulated functions. By understand the strengths and weaknesses of the cytoskeleton researchers can effectively treat cytoskeletal related diseases or find new ways to treat these diseases. ==

Fletcher, Daniel A., and R. Dyche Mullins. "Cell Mechanics And The Cytoskeleton."Nature 463.7280 (2010): 485-492. Print.

Nowak, K, K McCullagh, E Poon, and K Davies. "Muscular dystrophies related to the cytoskeleton/nuclear envelope.."NCBI 265 (2005): 98-111. Print.

Fletcher, Daniel A., and R. Dyche Mullins. "Cell Mechanics And The Cytoskeleton." Nature 463.7280 (2010): 485-492. Print.

"milestones timeline." Nature.com. Nature Publishing Group, n.d. Web. 1 Dec. 2013. 

Farah, Michelle E., Vladimir Sirotkin, Brian Haarer, David Kakhniashvili, and David C. Amberg. "Diverse protective roles of the actin cytoskeleton during oxidative stress." Cell and Molecular Biology 68.6 (2011): 340-354. Print.

Amano, Mutsuki, Masanori Nakayama, and Kozo Kaibuchi. "Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity." Cell & Molecular Biology 67.9 (2010): 545-554. Print. ==Carney, Bruce K., Victoria Caruso Silva, and Lynne Cassimeris. "The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53." Cell & Molecular Biology 69.5 (2012): 278-289. Print. ==