Forum Ph.D.
Joined: 30 Dec 2008
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Location: Nirgendwo und Ueberall
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Link to paper assignment is based on:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC317085/
In 1998, Eva Chin published a landmark paper in the journal Genes and Development. Her research group linked calcium (which makes muscles contract) to the expression of slow-twitch muscle fibers via the calcineurin pathway.
The calcineurin pathway works in the following way:
When calcium levels are low and sustained, calcium molecules bind to calmodulin and calcineurin (a phosphatase, or a phosphate removing compound). Calcineurin then removes a phosphate from a specific region of NFAT ( a transcription factor involved in the development of cardiac, skeletal muscle, and nervous systems), which results in a conformational change that exposes a nuclear localization signal resulting in NFAT nuclear import (the NFAT is altered and a part of it is now exposed, which draws it into the nucleus). Once inside the nucleus, NFAT can transcribe DNA into RNA via RNA polymerase (an enzyme) and then RNA will be translated into polypeptide chains (chains of amino acids) on ribosomes located in the rough endoplasmic reticulum.
Chin’s study showed that blocking calcineurin with cyclosporin A led to an increase in the percentage of fast-twitch fibres when one regularly exercises. Correspondingly, slow-twitch fibers (type I) were prevalent in those whose calcineurin pathways weren’t blocked. Motor nerve stimulation at 10–15 Hz, characteristic of slow-twitch fibers, lead to sustained (yet low) levels of calcium in cells and activated the calcineurin pathway. The illustration below shows this:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC317085/figure/F5/
The significance of the study is best stated by its author:
“Here we demonstrate that fiber-type-specific gene expression in skeletal muscles is controlled by a signaling mechanism that involves calcineurin, a cyclosporin-sensitive, calcium-regulated serine/threonine phosphatase. This discovery has considerable explanatory power, in that it elucidates plausibly a complete signaling pathway linking motor nerve activity to selective changes in gene expression that establish diversity among myofibers.”
The target audience for such research is anyone interested in genetics or exercise physiology. The study allows insight into the workings of the human body during exercise. Research scientists are the primary audience and they can build upon this work by learning how to a.) artificially promote conversion of muscle fibers to the desired type via drugs b.) learn more about the ways in which exercise can alter gene expression.
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plz...I want to know if I'm understanding things properly...