Trafficking and signalling of gonadotrophin-releasing hormone receptors: an automated imaging approach.
Gonadotrophin-releasing hormone (GnRH) is a neuropeptide that mediates central control of reproduction by stimulating gonadotrophin secretion from the pituitary. It acts via 7 transmembrane region (7TM) receptors that lack C-terminal tails, regions that for many 7TM receptors, are necessary for agonist-induced phosphorylation and arrestin binding as well as arrestin-dependent desensitization, internalization and signalling. Recent work has revealed that human GnRH receptors (GnRHR) are poorly expressed at the cell surface. This apparently reflects inefficient exit from the endoplasmic reticulum, which is thought to be increased by pharmacological chaperones (non-peptide GnRHR antagonists that increase cell surface GnRHR expression) or reduced by point mutations that further impair GnRHR trafficking and thereby cause infertility. Here, we review recent work in this field, with emphasis on the use of semi-automated imaging to interrogate compartmentalization and trafficking of these unique 7TM receptors.
Finch
A R
AR
University of Bristol, Labs. for Integrative Neuroscience and Endocrinology, Department of Clinical Sciences at South Bristol, Bristol, UK.
Sedgley
K R
KR
Armstrong
S P
SP
Caunt
C J
CJ
McArdle
C A
CA
D000818:Animals; D057205:Automation, Laboratory; D002460:Cell Line; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging; D015336:Molecular Probe Techniques; D011485:Protein Binding; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011966:Receptors, LHRH / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011966:Receptors, LHRH; D011993:Recombinant Fusion Proteins; C450520:seven-transmembrane G-protein-coupled receptor; D007987:Gonadotropin-Releasing Hormone