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Characterization of the novel h82r mutation in cgi-58 that causes neutral lipid storage disorder in humans
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Hassanien, Sarah. Characterization of the novel h82r mutation in cgi-58 that causes neutral lipid storage disorder in humans. Retrieved from https://doi.org/doi:10.7282/T37D2SN6

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TitleCharacterization of the novel h82r mutation in cgi-58 that causes neutral lipid storage disorder in humans
NameHassanien, Sarah (author); Brasaemle, Dawn L. (chair); Storch, Judith (internal member); Anthony, Tracy G. (internal member); Rutgers University; Graduate School - New Brunswick
Date Created2014
Other Date2014-10 (degree)
SubjectNutritional Sciences, Lipids--Metabolism--Disorders
Extent1 online resource (x, 58 p. : ill.)
DescriptionComparative 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.
NoteM.S.
NoteIncludes bibliographical references
Noteby Sarah Hassanien
Genretheses, ETD graduate
Persistent URLhttps://doi.org/doi:10.7282/T37D2SN6
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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