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Understanding the molecular mechanism of the fat signaling pathway in Drosophila melanogaster
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TitleInfo
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Title
Understanding the molecular mechanism of the fat signaling pathway in Drosophila melanogaster
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ETD_1827
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051817
Language
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eng
Genre
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theses
Subject
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(authority = RUETD)
Topic
Cell and Developmental Biology
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Cellular signal transduction
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Fat--Physiological aspects
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Drosophila melanogaster
Abstract
Fat is an atypical cadherin and regulates planar cell polarity (PCP) and imaginal disc growth. The Golgi kinase Four-jointed modulates the interaction of Fat and its potential ligand Dachsous and an unconvential myosin Dachs mediates nearly all Fat functions. The Hippo tumor suppressor pathway was demonstrated to regulate growth and cell death through the kinase Warts and transcription factor Yorkie. Genetically, the Hippo pathway is downstream of Fat, Dachs and the FERM-domain protein Expanded. The molecular basis was unknown how Fat interacts with Expanded and how Fat and Dachs regulate the Hippo pathway.
We found that Fat regulates Warts stability in a Dachs-dependent manner. Expanded and other tumor suppressors inluding Hippo, Mats and Salvador do not affect Warts levels, suggesting a distinct mechanism in regulating Warts. A casein kinase I δ/ε mutant, dco3 also destabilizes Warts, and genetically is upstream of dachs. The regulation of Warts by Fat and Expanded via different mechanisms was further validated by the additive effects of fat and expanded on imaginal disc growth and development. Mutation of fat also influences Expanded stability or subcellular localization through Dachs, indicating a crosstalk between Fat pathway and Expanded.
The significance of Warts in Fat and Expanded functions was demonstrated by our observation that mutations in either expanded or fat were rescued to viability by overexpressing Warts, indicating that reported effects on endocytosis or other pathways are not essential. These rescue experiments also separate the transcriptional from the PCP branches of Fat signaling and reveal that Expanded does not directly affect PCP.
We found that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N- and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, which is promoted by Dachsous. Dco is required for Fat signaling, and is able to phosphorylate the Fat intracellular domain in cultured cells, and is required for normal Fat phosphorylation in vivo. dco3 mutant affects Fat’s influence on growth and gene expression, but not its influence on PCP, suggesting separated growth and PCP pathways from Fat.
We found that Fat regulates Warts stability in a Dachs-dependent manner. Expanded and other tumor suppressors inluding Hippo, Mats and Salvador do not affect Warts levels, suggesting a distinct mechanism in regulating Warts. A casein kinase I δ/ε mutant, dco3 also destabilizes Warts, and genetically is upstream of dachs. The regulation of Warts by Fat and Expanded via different mechanisms was further validated by the additive effects of fat and expanded on imaginal disc growth and development. Mutation of fat also influences Expanded stability or subcellular localization through Dachs, indicating a crosstalk between Fat pathway and Expanded.
The significance of Warts in Fat and Expanded functions was demonstrated by our observation that mutations in either expanded or fat were rescued to viability by overexpressing Warts, indicating that reported effects on endocytosis or other pathways are not essential. These rescue experiments also separate the transcriptional from the PCP branches of Fat signaling and reveal that Expanded does not directly affect PCP.
We found that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N- and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, which is promoted by Dachsous. Dco is required for Fat signaling, and is able to phosphorylate the Fat intracellular domain in cultured cells, and is required for normal Fat phosphorylation in vivo. dco3 mutant affects Fat’s influence on growth and gene expression, but not its influence on PCP, suggesting separated growth and PCP pathways from Fat.
PhysicalDescription
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electronic resource
Extent
xv, 198 p. : ill.
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application/pdf
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text/xml
Note
Supplementary File: Supplementary material
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 185-197)
Note
(type = statement of responsibility)
by YongQiang Feng
Name
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Feng
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YongQiang
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1974
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author
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YongQiang Feng
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(type = family)
Edery
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Isaac
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chair
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Advisory Committee
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Isaac Edery
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(type = family)
Padgett
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Richard
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internal member
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Advisory Committee
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Richard W Padgett
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Steward
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Ruth
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internal member
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Advisory Committee
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Ruth Steward
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(type = family)
Irvine
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Kenneth
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internal member
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Kenneth D Irvine
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Matise
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Michael
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outside member
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Advisory Committee
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Michael P Matise
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
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2009
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2009-10
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xx
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Rutgers University Electronic Theses and Dissertations
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ETD
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
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doi:10.7282/T3GF0TNC
Genre
(authority = ExL-Esploro)
ETD doctoral
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(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
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Feng
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YongQiang
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Permission or license
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YongQiang Feng
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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