Modeling the Fusion and Severing of Neurofilament Polymers in Cells
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Date
2015-03-25
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Abstract
Neurofilaments are microscopic protein polymers that are abundant in the cytoplasm of nerve cells. They make up an important component of the cytoskeleton, which functions like an internal scaffold to give cells shape and mechanical strength. Neurofilaments are transported along axons and accumulate abnormally in many neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Alzheimer’s, and Charcot-Marie-Tooth Disease. These structural polymers can be very long and our lab has data showing that neurofilament length influences their transport; however, it is not known how neurofilament length is controlled. We hypothesize that neurofilament length is regulated by a dynamic cycle of fusion and severing. To test this proposal we used fluorescent tagging to create distinct red and green populations of neurofilaments in living cells. Neurofilament fusion results in the appearance of red-green polymer junctions while severing results in a decrease in the lengths of both red and green segment populations. We are currently in the process of quantifying fusion experimentally, and preliminary data confirms that annealing is frequent. To further explore our proposal we are using computational modeling built on stochastic simulation algorithms to mimic neurofilament length regulation behavior. By analyzing neurofilament length distributions and the frequency of red-green junctions, our model will help us determine if annealing and severing solely dictate neurofilament length regulation. We expect our study to reveal a novel mechanism for the regulation of neurofilament polymer length in nerve cells.
Description
Biological Sciences: 3rd Place (The Ohio State University Denman Undergraduate Research Forum)
Keywords
Neurofilaments, Modeling, Length Regulation, Stochastic Simulation Algorithm