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Characterization of the novel h82r mutation in cgi-58 that causes neutral lipid storage disorder in humans
Descriptive
TitleInfo
Title
Characterization of the novel h82r mutation in cgi-58 that causes neutral lipid storage disorder in humans
Name
(type = personal)
NamePart
(type = family)
Hassanien
NamePart
(type = given)
Sarah
NamePart
(type = date)
1989-
DisplayForm
Sarah Hassanien
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Brasaemle
NamePart
(type = given)
Dawn L.
DisplayForm
Dawn L. Brasaemle
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Storch
NamePart
(type = given)
Judith
DisplayForm
Judith Storch
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Anthony
NamePart
(type = given)
Tracy G.
DisplayForm
Tracy G. Anthony
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal 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)
2014-10
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Comparative gene identification-58 (CGI-58) interacts with and co-activates adipose triglyceride lipase (ATGL). The H82R mutation in human CGI-58 causes a neutral lipid storage disorder (NLSD) characterized by ichthyosis and excessive triacylglycerol storage in many types of cells. We studied the comparable H84R mutation in mouse CGI-58, and H84A mutated CGI-58, to ask how CGI-58 function is impaired. The ectopic expression of wild-type (WT) CGI-58 in human NLSD fibroblasts reduced excessive triglyceride storage to normal levels, whereas H84R CGI-58 was ineffective. Additionally, H84R CGI-58 failed to co-activate ATGL in an in vitro triglyceride hydrolase assay and H84A CGI-58 was not as efficient, when compared to WT CGI-58. Immunofluorescence microscopy revealed that H84R and H84A CGI-58 localized to ectopic perilipin 1A on lipid droplets of cultured NIH3T3CARΔ fibroblasts as well as WT CGI-58. Moreover, the addition of forskolin and isobutylmethylxanthine to the cells triggered the dispersion of all three variants of CGI-58 from the perilipin scaffold into the cytoplasm. A co-immunoprecipitation assay demonstrated that H84R and H84A CGI-58 bound ATGL as well as WT CGI-58. Additionally, while WT CGI-58 and ATGL can be individually recruited to lipid droplets and ATGL recruitment to lipid droplets is increased in the presence of CGI-58, the H84R and H82R mutations do not interfere with lipid droplet recruitment of CGI-58 with ATGL. Thus, although H84R CGI-58 shows appropriate subcellular localization in cells expressing perilipin 1A, binds to ATGL, and is effectively recruited to lipid droplets, it does not co-activate ATGL’s hydrolase activity. Future experiments are needed to explore additional mechanisms for deficient function of H84R CGI-58.
Subject
(authority = RUETD)
Topic
Nutritional Sciences
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_5919
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (x, 58 p. : ill.)
Note
(type = degree)
M.S.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Lipids--Metabolism--Disorders
Note
(type = statement of responsibility)
by Sarah Hassanien
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/T37D2SN6
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Hassanien
GivenName
Sarah
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2014-09-26 15:14:15
AssociatedEntity
Name
Sarah Hassanien
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.
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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