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Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster./
Author:	Schulman, Victoria Kalasinsky.
Description:	1 online resource (586 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 75-12, Section: B.
Contained By:	Dissertations Abstracts International75-12B.
Subject:	Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3580194click for full text (PQDT)
ISBN:	9781303889660

Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster.
Schulman, Victoria Kalasinsky.

Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster. - 1 online resource (586 pages)

Source: Dissertations Abstracts International, Volume: 75-12, Section: B.

Thesis (Ph.D.)--Weill Medical College of Cornell University, 2014.

Includes bibliographical references

Nuclei are precisely positioned within all cells, occupying distinct intracellular locations that serve to optimize cell function. Skeletal myofibers are multinucleated cells with peripherally located myonuclei that are evenly distributed throughout the myofiber to maximize internuclear distance. Disruptions to this arrangement of myonuclei are commonly found in tissue biopsies from patients with various muscle diseases. To better understand muscle disease, we study the process of myonuclear positioning in the conserved myofiber using Drosophila melanogaster as a model system. Myonuclear positioning is known to be a microtubule-dependent process, and we identified that the microtubule motor proteins, Kinesin and Dynein, are both required for proper myonuclear positioning. Moreover, a number of regulatory proteins influence the activity of each motor, including Kinesin light chain, Dynein light chain, Rapsynoid, CLIP-190, Lis-1, and Glued/p150. Additionally, Sunday Driver (Syd) is another type of regulator, known as a motor adaptor, which interacts with both Kinesin and Dynein to coordinate their activities and promote proper myonuclear positioning. Together, these proteins collectively work to position myonuclei via multiple mechanisms. Kinesin and Dynein work directly on the nucleus to promote myonuclear translocation. Kinesin also regulates the transport of Dynein to a distant location at the cell cortex, where Dynein activity mediates pulling of microtubules, and the attached myonuclei, into proper position. The latter mechanism requires Syd to mediate interactions between Kinesin and Dynein, but Syd only activates this pathway in response to intracellular cues from the JNK signaling pathway. Moreover, evidence suggests that these distinct mechanisms are temporally controlled, and we propose that Syd dictates a shift in motor protein activity from one pathway to the next. Finally, disruption of either pathway leads to muscle dysfunction, mimicking disease states in humans, but importantly, expression of JIP3, the mammalian ortholog of Syd, rescues both myonuclear position and locomotive ability. These data highlight the high degree of conservation across species and, thus, the utility of model organisms in elucidating precise cellular mechanisms that are directly applicable to mammalian biology. With these studies, we advanced the field of muscle biology and identified a number of proteins that, when disrupted, lead to disease phenotypes.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9781303889660Subjects--Topical Terms:

530508
Genetics.
Subjects--Index Terms:

DyneinIndex Terms--Genre/Form:

542853
Electronic books.

Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster.
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245 1 0 $a Cytoskeletal motors, cargo adaptors, and signaling cascades are required for proper myonuclear positioning and muscle function in Drosophila Melanogaster.
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300 $a 1 online resource (586 pages)
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500 $a Source: Dissertations Abstracts International, Volume: 75-12, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Baylies, Mary.
502 $a Thesis (Ph.D.)--Weill Medical College of Cornell University, 2014.
504 $a Includes bibliographical references
520 $a Nuclei are precisely positioned within all cells, occupying distinct intracellular locations that serve to optimize cell function. Skeletal myofibers are multinucleated cells with peripherally located myonuclei that are evenly distributed throughout the myofiber to maximize internuclear distance. Disruptions to this arrangement of myonuclei are commonly found in tissue biopsies from patients with various muscle diseases. To better understand muscle disease, we study the process of myonuclear positioning in the conserved myofiber using Drosophila melanogaster as a model system. Myonuclear positioning is known to be a microtubule-dependent process, and we identified that the microtubule motor proteins, Kinesin and Dynein, are both required for proper myonuclear positioning. Moreover, a number of regulatory proteins influence the activity of each motor, including Kinesin light chain, Dynein light chain, Rapsynoid, CLIP-190, Lis-1, and Glued/p150. Additionally, Sunday Driver (Syd) is another type of regulator, known as a motor adaptor, which interacts with both Kinesin and Dynein to coordinate their activities and promote proper myonuclear positioning. Together, these proteins collectively work to position myonuclei via multiple mechanisms. Kinesin and Dynein work directly on the nucleus to promote myonuclear translocation. Kinesin also regulates the transport of Dynein to a distant location at the cell cortex, where Dynein activity mediates pulling of microtubules, and the attached myonuclei, into proper position. The latter mechanism requires Syd to mediate interactions between Kinesin and Dynein, but Syd only activates this pathway in response to intracellular cues from the JNK signaling pathway. Moreover, evidence suggests that these distinct mechanisms are temporally controlled, and we propose that Syd dictates a shift in motor protein activity from one pathway to the next. Finally, disruption of either pathway leads to muscle dysfunction, mimicking disease states in humans, but importantly, expression of JIP3, the mammalian ortholog of Syd, rescues both myonuclear position and locomotive ability. These data highlight the high degree of conservation across species and, thus, the utility of model organisms in elucidating precise cellular mechanisms that are directly applicable to mammalian biology. With these studies, we advanced the field of muscle biology and identified a number of proteins that, when disrupted, lead to disease phenotypes.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
650 4 $a Genetics. $3 530508
650 4 $a Cellular biology. $3 3172791
650 4 $a Developmental biology. $3 592588
653 $a Dynein
653 $a Ensconsin
653 $a Kinesin
653 $a Microtubles
653 $a Muscle Nuclei
653 $a Sunday Drivers
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690 $a 0369
690 $a 0379
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710 2 $a ProQuest Information and Learning Co. $3 783688
710 2 $a Weill Medical College of Cornell University. $3 1021736
773 0 $t Dissertations Abstracts International $g 75-12B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3580194 $z click for full text (PQDT)