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dc.contributor.authorSalazar-De Simone, Glicella
dc.date.accessioned2018-07-12T17:38:33Z
dc.date.available2018-07-12T17:38:33Z
dc.date.issued2011
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 73-09(E), Section: B.;Advisors: Nancy Carrasco.
dc.identifier.urihttps://yulib002.mc.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3510870
dc.identifier.urihttps://hdl.handle.net/20.500.12202/1315
dc.description.abstractThe Na+/I- symporter (NIS) is the key plasma membrane glycoprotein that mediates active transport in the thyroid and other tissues. The Na+/monocarboxylate transporter (SMCT)---a highly homologous protein to NIS---is a plasma membrane protein that translocates nicotinate and other monocarboxylates in a variety of tissues.;Part I of this thesis focuses on structure/function relations in NIS. We demonstrated that residues L88, W89, L96, T101 and L103 in transmembrane segment (TMS) III of NIS are not critical for NIS function, whereas M90, Q94, and N97 participate in I- binding and/or translocation. Furthermore, our data indicate that M90 and Q94 are involved in the cation translocation pathway, and N97 is not, suggesting that both Na+ and I- start out on the same translocation pathway, but this pathway may bifurcate later on. Additionally, we have shown that although position 94 is predicted to be located within the TMS, it tolerates the negative charge imparted by Glu, consistent with the notion of position 94 being in a hydrophilic environment, consistent with our 3D homology model. We uncovered that position 94 plays a critical role in NIS substrate specificity and transport stoichiometry. In conclusion, these results provide detailed molecular information that may be useful for ongoing efforts to develop novel NIS clinical applications.;In part II of this thesis, we studied the role of the COOH-terminus of SMCT on the function and polarized targeting of the protein to the cell surface. We showed that, whereas the COOH-terminus of SMCT is not required for function, two portions of the cytoplasmic tail are important for targeting of the transporter to the plasma membrane. In addition, we have conclusively demonstrated that the last 155 amino acids of SMCT are not necessary for the transporter's function but are required for optimal activity. In polarized MDCK monolayers, we showed that, the COOH-terminus of SMCT is not involved in its polarized (apical) localization. Future studies are needed to establish what region of the SMCT sequence contains the information that directs its apical targeting, which will eventually prove helpful for identifying putative interacting proteins.
dc.publisherProQuest Dissertations & Theses
dc.subjectBiochemistry.
dc.subjectCellular biology.
dc.subjectBiophysics.
dc.titleNIS (sodium/iodine symporter) and SMCT (sodium/monocarboxylate transporter): a revealing comparison of two related proteins
dc.typeDissertation


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