Modern Methods to Investigate the Oligomerization of Glycoprotein Hormone Receptors (TSHR, LHR, FSHR)

2013 ◽  
pp. 367-383 ◽  
Author(s):  
Marco Bonomi ◽  
Luca Persani
Keyword(s):  
Hormone Receptors ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors ◽  
Modern Methods

scholarly journals Specificity and promiscuity of gonadotropin receptors

Reproduction ◽  
2005 ◽  
Vol 130 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Sabine Costagliola ◽  
Eneko Urizar ◽  
Fernando Mendive ◽  
Gilbert Vassart
Keyword(s):  
Hormone Receptors ◽  
Fsh Receptor ◽  
Ovarian Hyperstimulation ◽  
High Concentration ◽  
Glycoprotein Hormone ◽  
Functional Specificity ◽  
The Past ◽  
Glycoprotein Hormone Receptors ◽  
Naturally Occurring ◽  
Available Information

The dichotomy between hormone recognition by the ectodomain and activation of the G protein by the rhodopsin-like serpentine portion is a well established property of glycoprotein hormone receptors. The specificity barrier avoiding promiscuous activation of the FSH receptor by the high concentration of human chorionic gonadotropin (hCG) prevailing during human pregnancy was thus believed to lie in the ectodomain. In the past two years, mutations responsible for rare spontaneous cases of ovarian hyperstimulation syndromes have partially modified this simple view. Five naturally occurring mutations have been identified which cause an increase in the sensitivity of the FSH receptor to hCG. Surprisingly, these mutations are all located in the serpentine portion of the receptor. In addition to their effect on sensitivity to hCG, they increase sensitivity of the FSH receptor to TSH, and are responsible for activating the receptor constitutively. Together, the available information indicates that the ectodomain and the serpentine domain of the FSH receptor each contribute to the specificity barrier preventing its spurious activation by hCG. While the former is responsible for establishment of binding specificity, the latter introduces a novel notion of functional specificity.Recent data demonstrate that LH and FSH receptors can constitute functional homo- and heterodimers. This suggests the possibility that in cells co-expressing the two receptors, such as granulosa cells, the heterodimers might be endowed with functional characteristics different from those of each homodimer.

scholarly journals Characterization of Two Fly LGR (Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor) Proteins Homologous to Vertebrate Glycoprotein Hormone Receptors: Constitutive Activation of Wild-Type Fly LGR1 But Not LGR2 in Transfected Mammalian Cells**This study was supported by NIH Grant HD-23273. The GenBank submission number for fly LGR2 is AF274591.

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Shinya Nishi ◽  
Sheau Yu Hsu ◽  
Karen Zell ◽  
Aaron J. W. Hsueh
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Coupling Mechanism ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors ◽  
Signaling Mechanisms ◽  
G Protein Coupled

Abstract The receptors for lutropin (LH), FSH, and TSH belong to the large G protein-coupled receptor (GPCR) superfamily and are unique in having a large N-terminal extracellular (ecto-) domain important for interactions with the large glycoprotein hormone ligands. Recent studies indicated the evolution of a large family of the leucine-rich repeat-containing, G protein-coupled receptors (LGRs) with at least seven members in mammals. Based on the sequences of mammalian glycoprotein hormone receptors, we have identified a new LGR in Drosophila melanogaster and named it as fly LGR2 to distinguish it from the previously reported fly LH/FSH/TSH receptor (renamed as fly LGR1). Genomic analysis indicated the presence of 10 exons in fly LGR2 as compared with 16 exons in fly LGR1. The deduced fly LGR2 complementary DNA (cDNA) showed 43 and 64% similarity to the fly LGR1 in the ectodomain and transmembrane region, respectively. Comparison of 12 LGRs from diverse species indicated that these proteins can be divided into three subfamilies and fly LGR1 and LGR2 belong to different subfamilies. Potential signaling mechanisms were tested in human 293T cells overexpressing the fly receptors. Of interest, fly LGR1, but not LGR2, showed constitutive activity as reflected by elevated basal cAMP production in transfected cells. The basal activity of fly LGR1 was further augmented following point mutations of key residues in the intracellular loop 3 or transmembrane VI, similar to those found in patients with familial male precocious puberty. The present study reports the cloning of fly LGR2 and indicates that the G protein-coupling mechanism is conserved in fly LGR1 as compared with the mammalian glycoprotein hormone receptors. The characterization of fly receptors with features similar to mammalian glycoprotein hormone receptors allows a better understanding of the evolution of this unique group of GPCRs and future elucidation of their ligand signaling mechanisms.

scholarly journals The intramolecular agonist is obligate for activation of glycoprotein hormone receptors

2020 ◽  
Vol 34 (8) ◽  
pp. 11243-11256
Author(s):  
Annelie Schulze ◽  
Gunnar Kleinau ◽  
Susanne Neumann ◽  
Patrick Scheerer ◽  
Torsten Schöneberg ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors

scholarly journals A sea lamprey glycoprotein hormone receptor similar with gnathostome thyrotropin hormone receptor

2008 ◽  
Vol 41 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Mihael Freamat ◽  
Stacia A Sower
Keyword(s):  
Hormone Receptor ◽  
Hormone Receptors ◽  
Functional Divergence ◽  
Sea Lamprey ◽  
Glycoprotein Hormone ◽  
Receptor System ◽  
Glycoprotein Hormone Receptors ◽  
Molecular Phylogenetic ◽  
Synthetic Ligand ◽  
Glycoprotein Hormone Receptor

The specificity of the vertebrate hypothalamic–pituitary–gonadal and hypothalamic–pituitary–thyroid axes is explained by the evolutionary refinement of the specificity of expression and selectivity of interaction between the glycoprotein hormones GpH (FSH, LH, and TSH) and their cognate receptors GpH-R (FSH-R, LH-R, and TSH-R). These two finely tuned signaling pathways evolved by gene duplication and functional divergence from an ancestral GpH/GpH-R pair. Comparative analysis of the protochordate and gnathostome endocrine systems suggests that this process took place prior or concomitantly with the emergence of the gnathostome lineage. Here, we report identification and characterization of a novel glycoprotein hormone receptor (lGpH-R II) in the Agnathan sea lamprey. This 781 residue protein was found ∼43% identical with mammalian TSH-R and FSH-R representative sequences, and similarly with these two classes of mammalian receptors it is assembled from ten exons. A synthetic ligand containing the lamprey glycoprotein hormone β-chain tethered upstream of a mammalian α-chain activated the lGpH-R II expressed in COS-7 cells but in a lesser extent than lGpH-R I. Molecular phylogenetic analysis of vertebrate GpH-R protein sequences suggests a closer relationship between lGpH-R II and gnathostome thyrotropin receptors. Overall, the presence and characteristics of the lamprey glycoprotein hormone receptors suggest existence of a primitive functionally overlapping glycoprotein hormone/glycoprotein hormone receptor system in this animal.

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