The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Malin C. Lagerström - One of the best experts on this subject based on the ideXlab platform.
-
The chicken G protein-coupled receptor (GPCR)-ome
2006Co-Authors: Malin C. Lagerström, Helgi B. Schiöth, Anders R. Hellström, Thomas P. Larsson, Robert FredrikssonAbstract:G protein-coupled receptors (GPCR) are integral membrane proteins with seven α-helices that translate a remarkable diversity of signals into cellular responses. The superfamily of GPCRs is among the largest and most diverse protein families in vertebrates.We have searched the human genome for GPCRs and show that the family includes approximately 800 proteins, which can divided into five main families; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2 and Secretin. This study represents one of the first overall road maps of the GPCR family in a mammalian genome. Moreover, we identified eight novel members of the human Adhesion family which are characterized by long N-termini with various domains. We also investigated the GPCR repertoire of the chicken genome, where we manually verified a total of 557 chicken GPCRs. We detected several specific expansions and deletions that may reflect some of the functional differences between human and chicken.Substantial effort has been made over the years to find compounds that can bind and activate the melanocortin 4 receptor (MC4R). This receptor is involved in food intake and is thus an important target for antiobesity drugs. We used site-directed mutagenesis to insert micromolar affinity binding sites for zinc between transmembrane (TM) regions 2 and 3. We generated a molecular model of the human MC4R which suggests that a rotation of TM3 is important for activation of the MC4R.Furthermore, we present seven new vertebrate prolactin releasing Hormone receptors (PRLHRs) and show that they form two separate subtypes, PRLHR1 and PRLHR2. We performed a pharmacological characterization of the human PRLHR which showed that the receptor can bind neuropeptide Y (NPY) related ligands. We propose that an ancestral PRLH peptide has coevolved with a redundant NPY binding receptor, which then became PRLHR. This suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
-
origin of the prolactin releasing Hormone prlh receptors evidence of coevolution between prlh and a redundant neuropeptide y receptor during vertebrate evolution
Genomics, 2005Co-Authors: Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Davids Fridmanis, Tomas Holmquist, Jan Andersson, Yilin Yan, Terje Raudsepp, Rima ZoorobAbstract:We present seven new vertebrate homologs of the Prolactin-Releasing Hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have a relatively high evolutionary rate compared to receptors with fixed peptide preference, which could indicate a drastic change in binding preference, thus supporting this hypothesis. This report suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
-
The ancestry of the Prolactin-Releasing Hormone precursor.
Annals of the New York Academy of Sciences, 2005Co-Authors: Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Helgi B. SchiöthAbstract:The Prolactin-Releasing Hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.
Robert Fredriksson - One of the best experts on this subject based on the ideXlab platform.
-
The chicken G protein-coupled receptor (GPCR)-ome
2006Co-Authors: Malin C. Lagerström, Helgi B. Schiöth, Anders R. Hellström, Thomas P. Larsson, Robert FredrikssonAbstract:G protein-coupled receptors (GPCR) are integral membrane proteins with seven α-helices that translate a remarkable diversity of signals into cellular responses. The superfamily of GPCRs is among the largest and most diverse protein families in vertebrates.We have searched the human genome for GPCRs and show that the family includes approximately 800 proteins, which can divided into five main families; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2 and Secretin. This study represents one of the first overall road maps of the GPCR family in a mammalian genome. Moreover, we identified eight novel members of the human Adhesion family which are characterized by long N-termini with various domains. We also investigated the GPCR repertoire of the chicken genome, where we manually verified a total of 557 chicken GPCRs. We detected several specific expansions and deletions that may reflect some of the functional differences between human and chicken.Substantial effort has been made over the years to find compounds that can bind and activate the melanocortin 4 receptor (MC4R). This receptor is involved in food intake and is thus an important target for antiobesity drugs. We used site-directed mutagenesis to insert micromolar affinity binding sites for zinc between transmembrane (TM) regions 2 and 3. We generated a molecular model of the human MC4R which suggests that a rotation of TM3 is important for activation of the MC4R.Furthermore, we present seven new vertebrate prolactin releasing Hormone receptors (PRLHRs) and show that they form two separate subtypes, PRLHR1 and PRLHR2. We performed a pharmacological characterization of the human PRLHR which showed that the receptor can bind neuropeptide Y (NPY) related ligands. We propose that an ancestral PRLH peptide has coevolved with a redundant NPY binding receptor, which then became PRLHR. This suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
-
origin of the prolactin releasing Hormone prlh receptors evidence of coevolution between prlh and a redundant neuropeptide y receptor during vertebrate evolution
Genomics, 2005Co-Authors: Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Davids Fridmanis, Tomas Holmquist, Jan Andersson, Yilin Yan, Terje Raudsepp, Rima ZoorobAbstract:We present seven new vertebrate homologs of the Prolactin-Releasing Hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have a relatively high evolutionary rate compared to receptors with fixed peptide preference, which could indicate a drastic change in binding preference, thus supporting this hypothesis. This report suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
-
The ancestry of the Prolactin-Releasing Hormone precursor.
Annals of the New York Academy of Sciences, 2005Co-Authors: Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Helgi B. SchiöthAbstract:The Prolactin-Releasing Hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.
Takahisa Furukawa - One of the best experts on this subject based on the ideXlab platform.
-
Identification of G Protein-Coupled Receptors (GPCRs) in Primary Cilia and Their Possible Involvement in Body Weight Control
PLOS ONE, 2015Co-Authors: Yoshihiro Omori, Taro Chaya, Satoyo Yoshida, Shoichi Irie, Toshinori Tsujii, Takahisa FurukawaAbstract:Primary cilia are sensory organelles that harbor various receptors such as G protein-coupled receptors (GPCRs). We analyzed subcellular localization of 138 non-odorant GPCRs. We transfected GPCR expression vectors into NIH3T3 cells, induced ciliogenesis by serum starvation, and observed subcellular localization of GPCRs by immunofluorescent staining. We found that several GPCRs whose ligands are involved in feeding behavior, including Prolactin-Releasing Hormone receptor (PRLHR), neuropeptide FF receptor 1 (NPFFR1), and neuromedin U receptor 1 (NMUR1), localized to the primary cilia. In addition, we found that a short form of dopamine receptor D2 (DRD2S) is efficiently transported to the primary cilia, while a long form of dopamine receptor D2 (DRD2L) is rarely transported to the primary cilia. Using an anti-Prlhr antibody, we found that Prlhr localized to the cilia on the surface of the third ventricle in the vicinity of the hypothalamic periventricular nucleus. We generated the Npy2r-Cre transgenic mouse line in which Cre-recombinase is expressed under the control of the promoter of Npy2r encoding a ciliary GPCR. By mating Npy2r-Cre mice with Ift80 flox mice, we generated Ift80 conditional knockout (CKO) mice in which Npy2r-positive cilia were diminished in number. We found that Ift80 CKO mice exhibited a body weight increase. Our results suggest that Npy2r-positive cilia are important for body weight control.
Peter J. Sharp - One of the best experts on this subject based on the ideXlab platform.
-
Changes in Basal Hypothalamic Chicken Gonadotropin‐Releasing Hormone‐I and Vasoactive Intestinal Polypeptide Associated with a Photo‐Induced Cycle in Gonadal Maturation and Prolactin Secretion in Intact and Thyroidectomized Starlings (Sturnus vulgari
Journal of neuroendocrinology, 2002Co-Authors: A. Dawson, Richard Talbot, Ian C. Dunn, Peter J. SharpAbstract:Chicken gonadotropin-releasing Hormone-I (GnRH-I) and the avian Prolactin-Releasing Hormone, vasoactive intestinal polypeptide (VIP), were measured in the basal hypothalamus in male starlings during photo-induced gonadal growth and the subsequent development and maintenance of reproductive photorefractoriness. Comparisons were made with thyroidectomized birds, which maintain breeding condition irrespective of changes in photoperiod. In intact birds, basal hypothalamic GnRH-I increased four-fold after photostimulation and then decreased 115-fold over 12 weeks to values characteristic of long-term photorefractoriness. Pituitary and plasma prolactin increased after photostimulation, reaching peak values when the testes were regressing, and returned to low values in long-term photorefractory birds. Basal hypothalamic VIP did not change after photostimulation in intact birds. In photostimulated thyroidectomized birds, values for basal hypothalamic GnRH-I and VIP, and for pituitary and plasma prolactin, remained no different to those of nonphotostimulated intact birds. These observations confirm that reproductive photorefractoriness is related to a decrease in hypothalamic GnRH-I. However, photorefractoriness in terms of prolactin secretion is not similarly related to a decrease in basal hypothalamic VIP. The mechanisms responsible for the decrease in prolactin in long-term photorefractory birds and for the total lack of photoperiodic responses in thyroidectomized birds remain unresolved.
-
Prolactin receptor gene expression in the brain and peripheral tissues in broody and nonbroody breeds of domestic hen.
General and comparative endocrinology, 1998Co-Authors: T. Ohkubo, Richard Talbot, Minoru Tanaka, Kunio Nakashima, Peter J. SharpAbstract:Abstract The objective of this study was to establish whether the gene encoding prolactin receptor (PRLR) is expressed in the hypothalamus and peripheral tissues of the domestic chicken and, if so, to determine whether there are breed differences in the structure or expression of the gene which might account for the observation that broodiness does not occur in the White Leghorn hen but does occur in other breeds of domestic hens, including the bantam. A preliminary experiment demonstrated that the absence of broodiness in White Leghorns is not due to a lack of a prolactin response to the avian Prolactin-Releasing Hormone vasoactive intestinal polypeptide. The largest amounts of PRLR mRNA in the brain, which did not differ significantly between laying White Leghorns and bantams, were found in the pituitary gland and basal and preoptic hypothalamus. Small or nondetectable amounts were found in both breeds in the forebrain, cerebellum, and optic lobes. Prolactin receptor mRNA was widely distributed in peripheral tissues in both breeds, in the following descending order of abundance: kidney, leg skin, brood patch, duodenum, intestine > thyroid gland > adrenal gland, liver, ovary ⪢ adipose tissue > thymus, spleen > muscle > blood. Southern blotting analysis using four restriction enzymes and a chicken PRLR cDNA probe demonstrated identical digestion patterns for White Leghorn and bantam genomic DNA. Northern blotting analysis identified two sizes of chicken PRLR mRNA transcripts (7.5 and 3.3 kb) in hypothalami from laying White Leghorn and bantam hens. It is concluded that differences in the expression of broodiness in White Leghorn and bantam hens cannot be explained by differences in the amounts of PRLR mRNA in the hypothalamus or in the transcription or gross structure of the PRLR gene.
Helgi B. Schiöth - One of the best experts on this subject based on the ideXlab platform.
-
The chicken G protein-coupled receptor (GPCR)-ome
2006Co-Authors: Malin C. Lagerström, Helgi B. Schiöth, Anders R. Hellström, Thomas P. Larsson, Robert FredrikssonAbstract:G protein-coupled receptors (GPCR) are integral membrane proteins with seven α-helices that translate a remarkable diversity of signals into cellular responses. The superfamily of GPCRs is among the largest and most diverse protein families in vertebrates.We have searched the human genome for GPCRs and show that the family includes approximately 800 proteins, which can divided into five main families; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2 and Secretin. This study represents one of the first overall road maps of the GPCR family in a mammalian genome. Moreover, we identified eight novel members of the human Adhesion family which are characterized by long N-termini with various domains. We also investigated the GPCR repertoire of the chicken genome, where we manually verified a total of 557 chicken GPCRs. We detected several specific expansions and deletions that may reflect some of the functional differences between human and chicken.Substantial effort has been made over the years to find compounds that can bind and activate the melanocortin 4 receptor (MC4R). This receptor is involved in food intake and is thus an important target for antiobesity drugs. We used site-directed mutagenesis to insert micromolar affinity binding sites for zinc between transmembrane (TM) regions 2 and 3. We generated a molecular model of the human MC4R which suggests that a rotation of TM3 is important for activation of the MC4R.Furthermore, we present seven new vertebrate prolactin releasing Hormone receptors (PRLHRs) and show that they form two separate subtypes, PRLHR1 and PRLHR2. We performed a pharmacological characterization of the human PRLHR which showed that the receptor can bind neuropeptide Y (NPY) related ligands. We propose that an ancestral PRLH peptide has coevolved with a redundant NPY binding receptor, which then became PRLHR. This suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
-
The ancestry of the Prolactin-Releasing Hormone precursor.
Annals of the New York Academy of Sciences, 2005Co-Authors: Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Helgi B. SchiöthAbstract:The Prolactin-Releasing Hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.
