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You searched for +publisher:"Georgia Tech" +contributor:("Dr Harish Radhakrishna"). Showing records 1 – 2 of 2 total matches.

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Georgia Tech

1. Gokhale, Kavita Chandan. Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model.

Degree: PhD, Biology, 2005, Georgia Tech

Poly-Q expanded exon 1 of huntingtin (Q103) fused to GFP is toxic to yeast cells containing endogenous yeast prions, [PIN+] ([RNQ+]) and/or [PSI+], which presumably serve as aggregation nuclei. Propagation of yeast prions is modulated by the chaperones of Hsp100/70/40 complex. While some chaperones were reported to influence poly-Q aggregation in yeast, it was not clear whether they do it directly or via affecting yeast prions. Our data show that while dominant negative Hsp104 mutants antagonize poly-Q aggregation and toxicity by eliminating endogenous yeast prions, some mutant alleles of Hsp104 decreases size and ameliorate toxicity of poly-Q aggregates without affecting prion propagation. Elevated levels of the yeast Hsp40 proteins, Ydj1 and Sis1, exhibit opposite effects on poly-Q aggregation and toxicity without influencing prion propagation. Among the yeast Hsp70s, only overproduction of Ssa4 antagonized poly-Q toxicity. We have also isolated dominant Anti-poly-Q-toxicity (AQT) mutants counteracting poly-Q toxicity only in the absence of the major ubiquitin-conjugating enzyme Ubc4. Prion forming potential of other Q-rich proteins and influence of Q and P-rich regions on prion propagation were also studied. Our data connects poly-Q aggregation and toxicity to the stress defense pathway in yeast. As many stress-defense proteins are conserved between yeast and mammals, our data shed light on possible mechanisms modulating poly-Q aggregation and toxicity in mammalian cells. Advisors/Committee Members: Dr Harish Radhakrishna (Committee Member), Dr Jung Choi (Committee Member), Dr Nick Hud (Committee Member), Dr Roger Wartell (Committee Member), Dr Yury Chernoff (Committee Member).

Subjects/Keywords: Chaperones; Glutamine; Molecular chaperones; Prions; Yeast

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Gokhale, K. C. (2005). Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/6856

Chicago Manual of Style (16th Edition):

Gokhale, Kavita Chandan. “Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model.” 2005. Doctoral Dissertation, Georgia Tech. Accessed January 19, 2021. http://hdl.handle.net/1853/6856.

MLA Handbook (7th Edition):

Gokhale, Kavita Chandan. “Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model.” 2005. Web. 19 Jan 2021.

Vancouver:

Gokhale KC. Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1853/6856.

Council of Science Editors:

Gokhale KC. Interactions between endogenous prions, chaperones and polyglutamine proteins in the yeast model. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/6856


Georgia Tech

2. Jones, Kymry Thereasa. The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor.

Degree: PhD, Biology, 2007, Georgia Tech

The muscarinic acetylcholine type 2 receptor (M2 mAChR), a member of the GPCR superfamily, is found throughout the parasympathetic nervous system where it controls pulmonary, urinary, and cardiac function, and neurotransmission. The molecular mechanisms that regulate M2 mAChR availability at the cell surface are an important component in controlling these physiological events. Since beta-arrestin proteins are known to regulate the activity of other GPCRs, we sought to identify their role in regulating M2 mAChR activity, a topic that remains contentious in the field. To achieve this goal we utilized mouse embryonic fibroblasts (MEFs) derived from beta-arrestin knockout mice lacking one or both isoforms (MEF KO1, KO2, or KO1/2 cells) in addition to exogenous expression of beta-arrestin mutants. This study demonstrates that agonist-induced internalization of M2 mAChR is beta-arrestin- and clathrin-dependent, and that the receptor stably co-localizes with beta-arrestin in early endosomal vesicles suggesting it behaves as a class B receptor. Next, we sought to identify beta-arrestin s function in regulating the post-endocytic trafficking (down-regulation) of the M2 mAChR. MEF KO1/2 cells were unable to down-regulate M2 mAChRs whereas MEF KO1 or KO2 cells retained the ability to do so. In MEFwt cells, both M2 mAChR and beta-arrestin exhibited basal ubiquitination that increased following agonist stimulation. Receptor degradation appeared to be regulated by the ubiquitination status of beta-arrestin 2, since expression of a chimeric รข-arrestin 2 form fused to ubiquitin increased both constitutive and agonist-promoted down-regulation, whereas expression of a beta-arrestin 2 mutant lacking putative ubiquitination sites, beta-arrestin 2K18R, K107R, K108R, K207R, K296R, significantly blocked degradation while internalization and stable association remained intact. Upon further analysis, the beta-arrestin 2K18R, K107R, K108R, K207R, K296R mutant blocked delivery of M2 mAChR to the late endosome/lysosome, presumably where degradation occurs. Inhibition of proteasome-dependent recycling of ubiquitin blocked receptor down-regulation without affecting internalization or the ubiquitination state of the M2 mAChR while ubiquitination of beta-arrestin 2 diminished significantly. These results support a role for ubiquitinated beta-arrestin in mediating M2 mAChR sorting and degradation in the lysosome. Collectively, these studies give us new insight on the function of beta-arrestin in regulating the activity of the M2 mAChR. Advisors/Committee Members: Dr. Nael A. McCarty (Committee Chair), Dr. Darrell Jackson (Committee Co-Chair), Dr. Alfred H. Merrill (Committee Member), Dr. Barbara D. Boyan (Committee Member), Dr. Harish Radhakrishna (Committee Member), Dr. Marion B. Sewer (Committee Member).

Subjects/Keywords: Muscarinic; GPCR; Receptor trafficking; Ubiquitination; Internalization; Down-regulation; Muscarinic receptors; Acetylcholine Receptors; Biological control systems

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jones, K. T. (2007). The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/24815

Chicago Manual of Style (16th Edition):

Jones, Kymry Thereasa. “The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor.” 2007. Doctoral Dissertation, Georgia Tech. Accessed January 19, 2021. http://hdl.handle.net/1853/24815.

MLA Handbook (7th Edition):

Jones, Kymry Thereasa. “The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor.” 2007. Web. 19 Jan 2021.

Vancouver:

Jones KT. The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor. [Internet] [Doctoral dissertation]. Georgia Tech; 2007. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1853/24815.

Council of Science Editors:

Jones KT. The role of beta-arrestin in regulating the muscarinic acetylcholine type II receptor. [Doctoral Dissertation]. Georgia Tech; 2007. Available from: http://hdl.handle.net/1853/24815

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