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Analysis of TGFβ receptor trafficking and signaling

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TitleInfo
Title
Analysis of TGFβ receptor trafficking and signaling
Name (type = personal)
NamePart (type = family)
Gleason
NamePart (type = given)
Ryan Joseph
NamePart (type = date)
1982-
DisplayForm
Ryan Gleason
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Grant
NamePart (type = given)
Barth D.
DisplayForm
Barth D. Grant
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Driscoll
NamePart (type = given)
Monica
DisplayForm
Monica Driscoll
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Padgett
NamePart (type = given)
Richard W.
DisplayForm
Richard W. Padgett
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Kramer
NamePart (type = given)
Sunita
DisplayForm
Sunita Kramer
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Members of the transforming growth factor β (TGFβ) superfamily function in a compelling array of developmental processes. This family of secreted ligands, as well as the signal transduction pathway, are highly conserved across metazoan biology. Due to this high level of conservation, the work described in this dissertation utilizes C. elegans as a genetic model organism to further elucidate fundamental mechanisms of TGFβ signaling. The Sma/Mab pathway, a conserved TGFβ pathway, regulates diverse developmental programs such as body size and innate immunity, among others. We performed a microarray study to uncover a system wide analysis of how such diverse developmental programs are executed. Consistent with the regulation of body size by the pathway, genes involved in protein synthesis, degradation, and metabolism were upregulated by Sma/Mab signaling. In addition, genes involved in innate immunity were also positively regulated by the pathway. Transport of the TGFβ receptors from the plasma membrane to endosomes has been proposed to promote TGFβ signal transduction and shape ligand gradients throughout development. However, how the postendocytic trafficking of TGFβ receptors contributes to the regulation of signal transduction has remained enigmatic. In this study we set out to identify the molecular sorting complexes that regulate the TGFβ receptors’ recycling and to determine how receptor recycling affects signaling. Our in vivo results provide evidence that clathrindependent endocytosis is necessary for TGFβ signaling in C. elegans. Furthermore, we find that after internalization, two distinct recycling pathways regulate the transport of the type I and type II receptors back to the cell surface. Recycling of the type I receptor is regulated by the retromer complex, whereas the type II receptor is recycled via a distinct recycling pathway regulated by ARF-6. Genetic screens performed in our lab based on the Sma body size phenotype have uncovered several TGFβ signaling components. From this screen sma-10(wk88) has been characterized as a positive regulator of TGFβ signaling. I have shown that SMA-10 regulates the intracellular trafficking of the type I and type II TGFβ receptors. Furthermore, my studies show that SMA-10 localizes to both early and late endosomes.
Subject (authority = RUETD)
Topic
Cell and Developmental Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5402
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiii, 137 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Ryan Joseph Gleason
Subject (authority = ETD-LCSH)
Topic
Transforming growth factors-beta
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3N29V7K
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Gleason
GivenName
Ryan
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-04-07 23:03:11
AssociatedEntity
Name
Ryan Gleason
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2016-05-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 30th, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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