β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor

 

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dc.contributor.advisor Katz, Arieh en_ZA
dc.contributor.advisor Katz, Arieh en_ZA
dc.contributor.author Nkwayana, Nonhlanhla en_ZA
dc.date.accessioned 2014-07-28T14:57:48Z
dc.date.available 2014-07-28T14:57:48Z
dc.date.issued 2006 en_ZA
dc.identifier.citation Nkwayana, N. 2006. β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/3178
dc.description Includes abstract.
dc.description Includes bibliographical references.
dc.description Includes bibliographical references (leaves 74-81).
dc.description.abstract Over-expression of β-arrestin 1 in COS-l cells revealed that the mammalian type GnRH receptor can internalise in a β-arrestin dependent manner whereas the internalisation of the mammalian type I GnRH receptor is β-arrestin independent. investigate which domains on the mammalian type II GnRH receptor are required for β~arrestin dependent internalisation, chimeric receptors were created. en_ZA
dc.description.abstract The mammalian type II GnRH receptor possesses an intracellular C-terminal tail that is known to play a role in desensitisation, internalisation and overall signalling in GPCRs. On the other hand, the mammalian type I GnRH receptor, which lacks a C-terminal tail, does not readily desensitise and undergoes slow internalisation compared to the mammalian type II GnRH receptor. Over-expression of ß-arrestin 1 in COS-l cells revealed that the mammalian type GnRH receptor can internalise in a ß-arrestin dependent manner whereas the internalisation of the mammalian type I GnRH receptor is ß-arrestin independent. investigate which domains on the mammalian type II GnRH receptor are required for ß-arrestin dependent internalisation, chimeric receptors were created. Firstly, a chimera in which the full length type II GnRH receptor C-terminal tail was added to the tail-less type I GnRH receptor (TI/T2tail) was created. This chimera internalised in a ß-arrestin and GRK dependent manner, demonstrating that the type II GnRH receptor C-terminal tail confers ß-arrestin JGRK dependent internalisation on the originally ß-arrestin/GRK insensitive GnRH receptor. Mutating the putative GRK and casein kinase phosphorylation sites (serines 338 and 339) on the C-terminal tail of TI/T2tail to alanine residues did not abolish ß-arrestin dependent internalisation but eliminated GRK dependent internalisation, suggesting that other regions on the C-terminal tail are required for ß-arrestin dependent internalisation. A second chimera, in which the whole third intracellular loop of the type II GnRH receptor was replaced with that of the type I GnRH receptor (T2/TIICL3), was created. This chimera could not utilise ß-arrestin in its internalisation, indicating that the third intracellular loop of the type II GnRH receptor is required for ß-arrestin dependent internalisation. An alignment of the amino acid sequences of the two mammalian GnRH receptor third intracellular loops identified a basic residue rich area (R234, R236 and K237) on the type II GnRH receptor that was absent on the type I GnRH receptor. Interestingly, the triple mutant (R234,236,K237 A) still internalised in a ß-arrestin dependent manner, however, truncation of the C-terminal tail of R234,236,K237A abolished the ability of the receptor to internalise in a ß-arrestin dependent manner. This result indicated that the C-terminal tail of the type II GnRH receptor was compensating for the absence of the three basic residues. To summarise, this thesis demonstrates that the C-terminal tail of the type II GnRH receptor can confer ß-arrestin dependent intemalisation on the type I GnRH receptor. Furthermore, the third intracellular loop, and more specifically, basic residues R234, R236 and K237 on the mammalian type II GnRH receptor are required for ß-arrestin dependent intemalisation. en_ZA
dc.language.iso eng en_ZA
dc.subject.other Clinical Laboratory Sciences en_ZA
dc.title β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor en_ZA
dc.type Master Thesis
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Clinical Laboratory Sciences en_ZA
dc.type.qualificationlevel Masters
dc.type.qualificationname MSc en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Nkwayana, N. (2006). <i>β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/3178 en_ZA
dc.identifier.chicagocitation Nkwayana, Nonhlanhla. <i>"β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2006. http://hdl.handle.net/11427/3178 en_ZA
dc.identifier.vancouvercitation Nkwayana N. β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2006 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3178 en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Nkwayana, Nonhlanhla AB - Over-expression of β-arrestin 1 in COS-l cells revealed that the mammalian type GnRH receptor can internalise in a β-arrestin dependent manner whereas the internalisation of the mammalian type I GnRH receptor is β-arrestin independent. investigate which domains on the mammalian type II GnRH receptor are required for β~arrestin dependent internalisation, chimeric receptors were created. DA - 2006 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor TI - β-arrestin interacting domains on the type II gonadotropin-releasing hormone (GnRH) receptor UR - http://hdl.handle.net/11427/3178 ER - en_ZA


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