Characterization of Structure and Function Relationship between Domains of the ER Membrane Protein Atlastin

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dc.contributor.advisorMcNew, James A.en_US
dc.contributor.committeeMemberHuang, Huey W.en_US
dc.contributor.committeeMemberBraam, Janeten_US
dc.contributor.committeeMemberStern, Michaelen_US
dc.contributor.committeeMemberLwigale, Peter Yunjuen_US
dc.creatorDesai, Tanvien_US
dc.date.accessioned2014-08-05T20:51:15Zen_US
dc.date.available2014-08-05T20:51:15Zen_US
dc.date.created2014-05en_US
dc.date.issued2014-02-06en_US
dc.date.submittedMay 2014en_US
dc.date.updated2014-08-05T20:51:15Zen_US
dc.description.abstractThe endoplasmic Reticulum (ER) is an important site for lipid synthesis, protein synthesis and transport. ER fusion is an essential process for its maintenance and biogenesis. Mutations in genes involved in this process cause Hereditary Spastic Paraplegia (HSP). These mutations are shown to affect intracellular trafficking and localization of membrane compartment. One of the important proteins causing early onset of HSP is Atlastin. Previous work in McNew lab at Rice University (Moss et al., 2011b) has shown that atlastin is involved in the homotypic fusion of the ER and the C-terminal cytoplasmic region of atlastin is essential for atlastin mediated fusion. During my studies presented in this thesis, I was able to demonstrate that the C-terminal cytoplasmic region of atlastin destabilizes lipid bilayers to facilitate fusion. The requirement of C-terminal cytoplasmic region is minimal when fusing two fluid (or unstable) lipid bilayers. The C-terminal cytoplasmic region of atlastin forms an amphipathic helix and mutations on the hydrophobic phase of the helix reduce fusion. These mutations are not dominant, as presence of full length atlastin on even one of the fusing lipid bilayers can significantly improve fusion during a heterotypic fusion reaction. Additionally, domain swaps between human atlastin-1 and drosophila atlastin show that the role of C-terminal cytoplasmic region is highly conserved. Also, during my research presented here in, I found that when the transmembrane region and C-terminal cytoplasmic region of human atlastin-1 were swapped with drosophila atlastin, it showed functional similarity. These results show that although atlastins in organisms play an important role in the ER fusion, there are likely species specific differences in how this is achieved. An understanding of atlastin mediated fusion should help in unraveling mechanisms of HSP pathogenesis and other disorders arising from dysfunctional ER.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationDesai, Tanvi. "Characterization of Structure and Function Relationship between Domains of the ER Membrane Protein Atlastin." (2014) Diss., Rice University. <a href="https://hdl.handle.net/1911/76430">https://hdl.handle.net/1911/76430</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/76430en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectMembrane fusionen_US
dc.subjectMembrane proteinen_US
dc.subjectAtlastinen_US
dc.subjectEndoplasmic reticulumen_US
dc.subjectHereditary spastic paraplegiaen_US
dc.subjectIntracellular fusionen_US
dc.subjectAxonal neuropathyen_US
dc.titleCharacterization of Structure and Function Relationship between Domains of the ER Membrane Protein Atlastinen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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