SFE2001 Poster Presentations Signalling (4 abstracts)
A Threonine-Doublet within the Carboxyl-Terminal Tail of a Non-Mammalian Gonadotropin-Releasing Hormone Receptor is Critical for Rapid Agonist-Induced Internalization
AJ Pawson 1,2 , J Lopes 2 , AA Katz 2 , SR Maudsley 1 , R Sellar 1 , N Miller 1 , Y-M Sun 2 , RP Millar 1,2 & JS Davidson 2
1Human Reproductive Sciences Unit, Medical Research Council, Edinburgh, United Kingdom; 2Departments of Chemical Pathology and Medical Biochemistry, University of Cape Town Medical School, Cape Town, South Africa.
The chicken gonadotropin-releasing hormone receptor (cGnRH-R) is notable for having a cytoplasmic carboxyl-terminal tail, which is not present in the mammalian GnRH-Rs. We have previously shown that the cGnRH-R undergoes rapid agonist-induced internalization, and requires the carboxyl-terminal tail for this process. To investigate the role of the carboxyl-terminal tail of the cGnRH-R in relation to its rapid internalization, and to identify the key residues involved, a series of mutant constructs were generated, whereby either the tail was progressively truncated, or serine and threonine residues located in the tail substituted with alanine. Truncations of the carboxyl-terminal tail resulted in receptors that internalized GnRH agonist at a slower rate, and to a lower extent than the wild type receptor. Our data demonstrate the presence of signals for agonist-induced internalization in two regions, from Ser337 to Ser346, and Asp356 to the carboxyl-terminus. We show that a threonine-doublet located near the carboxyl-terminus plays a critical role in mediating rapid internalization. Furthermore, we provide evidence to suggest that the cGnRH-R expressed in COS-7 cells preferentially undergoes rapid agonist-induced internalization in caveolae, in a dynamin-dependent manner. Additionally, cGnRH-Rs are mobilized to the beta-arrestin- and clathrin-coated vesicle-mediated endocytic pathway upon beta-arrestin overexpression.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more