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Troponin C Isoforms Influence Stretch Activation and Mechanical Properties of Drosophila Muscles.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Troponin C Isoforms Influence Stretch Activation and Mechanical Properties of Drosophila Muscles./
Author:	Eldred, Catherine.
Description:	1 online resource (100 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 76-05, Section: B.
Contained By:	Dissertations Abstracts International76-05B.
Subject:	Biochemistry. -
Online resource:	click for full text (PQDT)
ISBN:	9781321312287

Troponin C Isoforms Influence Stretch Activation and Mechanical Properties of Drosophila Muscles.
Eldred, Catherine.

Troponin C Isoforms Influence Stretch Activation and Mechanical Properties of Drosophila Muscles. - 1 online resource (100 pages)

Source: Dissertations Abstracts International, Volume: 76-05, Section: B.

Thesis (Ph.D.)--Rensselaer Polytechnic Institute, 2014.

Includes bibliographical references

In order to survive, animals have evolved uncountable of ways to perform life functions. Some have longer leg bones, to cover more ground with each stride to be better adapted to chase and capture nourishing prey. Some have especially strong hind legs to quickly and effectively dig holes into which to escape from predators as well as the dexterity to evade capture. Others have evolved physiological enhancements which enable a smaller amount of muscle to generate more power or force per unit that they would otherwise be capable, enabling such functions as flight and the efficient and consistent beating of a heart. It is these physiological power enhancements that most interest me, and are the focus of this study. Flying insects have developed means to optimize their power output in their flight muscles to enable the smallest possible set of muscles to reliably lift the body mass of the insect and maneuver in flight. Some of these adaptations phenotypically correspond to biochemical adaptations evolved by vertebrate hearts to beat efficiently when rest or failure is not possible. One of those adaptations is stretch activation, which has been suggested to be physiologically relevant in the progression of heart disease. Homologies exist between the two systems, which make insect flight muscles a good fit for heart disease research. In my research, I investigated troponin C 4 (TnC4), a single-calcium binding isoform of troponin C (TnC) that exists in insect indirect flight muscle (IFM) and its potential link to stretch activation (SA), as well as troponin C 1 (TnC1), another IFM-specific isoform of TnC and its potential link to isometric tension. The model organism used in these studies was Drosophila. To evaluate the effect of each of these isoforms on SA, RNAi was used to knock down one or the other isoform, generating a fly with IFM deficient in the knocked down isoform. The effect of various levels of Ca2+ on the function of the IFM with one TnC isoform knocked down was then evaluated mechanically and histologically. What was found was not fully what was expected. When TnC4 was knocked down below the detection level, the muscle fiber had poor ultrastructural arrangement and was incapable of generating meaningful mechanical data; this likely indicates that TnC4 fulfills some kind of structural function during pupal rearrangement of the IFMs, which had not been observed before. TnC1 knockdown fibers demonstrated no differences mechanically from the wild-type, a situation significantly different from that found in troponin exchange studies in Lethocerus IFMs in recent publications, where the presence of TnC1 only corresponded to isometric tension and TnC4 only to stretch activation, but very little isometric tension. An unexpected, but significant finding of this study was that knockdown of one isoform or the other resulted in upregulation of the remaining isoform so that total TnC in the muscle remained unchanged from wild-type. On discovering that the TnC4 knockdown was not going to be useful for investigation into TnC4 function, it was decided to take steps to develop a new Drosophila line, to be null for the TnC4 gene. Success on this project would allow for the incorporation of TnC constructs in IFM more effectively in Drosophila to perform studies that will pinpoint the function of single TnC4 residues within the thin filament regulatory components of IFM, which is a more sophisticated set of experiments than had been possible in the past using only troponin exchange and RNAi along with muscle mechanics techniques.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9781321312287Subjects--Topical Terms:

582831
Biochemistry.
Subjects--Index Terms:

CardiomyopathyIndex Terms--Genre/Form:

554714
Electronic books.

Troponin C Isoforms Influence Stretch Activation and Mechanical Properties of Drosophila Muscles.
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520 $a In order to survive, animals have evolved uncountable of ways to perform life functions. Some have longer leg bones, to cover more ground with each stride to be better adapted to chase and capture nourishing prey. Some have especially strong hind legs to quickly and effectively dig holes into which to escape from predators as well as the dexterity to evade capture. Others have evolved physiological enhancements which enable a smaller amount of muscle to generate more power or force per unit that they would otherwise be capable, enabling such functions as flight and the efficient and consistent beating of a heart. It is these physiological power enhancements that most interest me, and are the focus of this study. Flying insects have developed means to optimize their power output in their flight muscles to enable the smallest possible set of muscles to reliably lift the body mass of the insect and maneuver in flight. Some of these adaptations phenotypically correspond to biochemical adaptations evolved by vertebrate hearts to beat efficiently when rest or failure is not possible. One of those adaptations is stretch activation, which has been suggested to be physiologically relevant in the progression of heart disease. Homologies exist between the two systems, which make insect flight muscles a good fit for heart disease research. In my research, I investigated troponin C 4 (TnC4), a single-calcium binding isoform of troponin C (TnC) that exists in insect indirect flight muscle (IFM) and its potential link to stretch activation (SA), as well as troponin C 1 (TnC1), another IFM-specific isoform of TnC and its potential link to isometric tension. The model organism used in these studies was Drosophila. To evaluate the effect of each of these isoforms on SA, RNAi was used to knock down one or the other isoform, generating a fly with IFM deficient in the knocked down isoform. The effect of various levels of Ca2+ on the function of the IFM with one TnC isoform knocked down was then evaluated mechanically and histologically. What was found was not fully what was expected. When TnC4 was knocked down below the detection level, the muscle fiber had poor ultrastructural arrangement and was incapable of generating meaningful mechanical data; this likely indicates that TnC4 fulfills some kind of structural function during pupal rearrangement of the IFMs, which had not been observed before. TnC1 knockdown fibers demonstrated no differences mechanically from the wild-type, a situation significantly different from that found in troponin exchange studies in Lethocerus IFMs in recent publications, where the presence of TnC1 only corresponded to isometric tension and TnC4 only to stretch activation, but very little isometric tension. An unexpected, but significant finding of this study was that knockdown of one isoform or the other resulted in upregulation of the remaining isoform so that total TnC in the muscle remained unchanged from wild-type. On discovering that the TnC4 knockdown was not going to be useful for investigation into TnC4 function, it was decided to take steps to develop a new Drosophila line, to be null for the TnC4 gene. Success on this project would allow for the incorporation of TnC constructs in IFM more effectively in Drosophila to perform studies that will pinpoint the function of single TnC4 residues within the thin filament regulatory components of IFM, which is a more sophisticated set of experiments than had been possible in the past using only troponin exchange and RNAi along with muscle mechanics techniques.
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