38 results found
Hanyaloglu AC, Grammatopoulos DK, 2017, Pleiotropic GPCR signaling in health and disease., Mol Cell Endocrinol, Vol: 449, Pages: 1-2
Jonas KC, Hanyaloglu AC, 2017, Impact of G protein-coupled receptor heteromers in endocrine systems, MOLECULAR AND CELLULAR ENDOCRINOLOGY, Vol: 449, Pages: 21-27, ISSN: 0303-7207
Owens LA, Abbara A, Lerner A, et al., 2017, The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function., Hum Reprod, Pages: 1-11
STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS. WHAT IS KNOWN ALREADY: hCG is the most widely used trigger of oocyte maturation, but is associated with an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a novel therapeutic option that safely triggers oocyte maturation even in women at high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also expressed in the human ovary, but there is limited data on the direct action of kisspeptin on the ovary. STUDY DESIGN SIZE, DURATION: Forty-eight women undergoing IVF treatment for infertility consented to kisspeptin-54 triggering and/or granulosa cell collection and were included in the study. Twelve women received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger oocyte maturation. In the kisspeptin-54 group, 12 received one injection of kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a 10 h interval (9.6 nmol/kg × 2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was aspirated and pooled from follicles during the retrieval of oocytes for IVF/ICSI. GL
Sposini S, Hanyaloglu AC, 2017, Spatial encryption of G protein-coupled receptor signaling in endosomes; Mechanisms and applications., Biochem Pharmacol, Vol: 143, Pages: 1-9
Within any cellular signaling system membrane trafficking is a critical mechanism for cells to translate complex networks into specific downstream responses, including the signal pathways activated by the superfamily of G protein-coupled receptors (GPCRs). Classically, membrane trafficking is viewed as a mechanism to regulate ligand sensitivity of a target tissue by controlling the level of surface receptors. Recent studies, however, have not only highlighted that GPCR trafficking is a tightly regulated process critical for spatio-temporal control of signaling, but that heterotrimeric G protein signaling can also be reactivated or continue to signal from distinct endocytic compartments, and even endosomal microdomains. The significance of spatio-temporal control will be discussed, not only with respect to how these novel molecular pathways impact our basic understanding of cellular regulation, but also our view of how aberrant signaling can result in disease. Furthermore, these mechanisms offer the potential application for novel therapeutic strategies to identify GPCR compounds with high specificity in their actions.
Sposini S, Jean-Alphonse FG, Ayoub MA, et al., 2017, Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms, Cell Reports, Vol: 21, Pages: 2855-2867, ISSN: 2211-1247
Endocytic trafficking is a critical mechanism for cells to decode complex signaling pathways, including those activated by G-protein-coupled receptors (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be spatially restricted between early endosomes (EEs) and the recently discovered endosomal compartment, the very early endosome (VEE). However, the molecular machinery driving GPCR activity from the VEE is unknown. Using luteinizing hormone receptor (LHR) as a prototype GPCR for this compartment, along with additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1 in rapid recycling and endosomal cAMP signaling without impacting the EE-localized β2-adrenergic receptor. LHR recycling is driven by receptor-mediated Gαs/cAMP signaling from the VEE and PKA-dependent phosphorylation of APPL1 at serine 410. Receptor/Gαs endosomal signaling is localized to microdomains of heterogeneous VEE populations and regulated by APPL1 phosphorylation. Our study uncovers a highly integrated inter-endosomal communication system enabling cells to tightly regulate spatially encoded signaling.
Babinsky VN, Hannan FM, Gorvin CM, et al., 2016, Allosteric Modulation of the Calcium-sensing Receptor Rectifies Signaling Abnormalities Associated with G-protein α-11 Mutations Causing Hypercalcemic and Hypocalcemic Disorders., J Biol Chem, Vol: 291, Pages: 10876-10885
Germline loss- and gain-of-function mutations of G-protein α-11 (Gα11), which couples the calcium-sensing receptor (CaSR) to intracellular calcium (Ca(2+) i) signaling, lead to familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2), respectively, whereas somatic Gα11 mutations mediate uveal melanoma development by constitutively up-regulating MAPK signaling. Cinacalcet and NPS-2143 are allosteric CaSR activators and inactivators, respectively, that ameliorate signaling disturbances associated with CaSR mutations, but their potential to modulate abnormalities of the downstream Gα11 protein is unknown. This study investigated whether cinacalcet and NPS-2143 may rectify Ca(2+) i alterations associated with FHH2- and ADH2-causing Gα11 mutations, and evaluated the influence of germline gain-of-function Gα11 mutations on MAPK signaling by measuring ERK phosphorylation, and assessed the effect of NPS-2143 on a uveal melanoma Gα11 mutant. WT and mutant Gα11 proteins causing FHH2, ADH2 or uveal melanoma were transfected in CaSR-expressing HEK293 cells, and Ca(2+) i and ERK phosphorylation responses measured by flow-cytometry and Alphascreen immunoassay following exposure to extracellular Ca(2+) (Ca(2+) o) and allosteric modulators. Cinacalcet and NPS-2143 rectified the Ca(2+) i responses of FHH2- and ADH2-associated Gα11 loss- and gain-of-function mutations, respectively. ADH2-causing Gα11 mutations were demonstrated not to be constitutively activating and induced ERK phosphorylation following Ca(2+) o stimulation only. The increased ERK phosphorylation associated with ADH2 and uveal melanoma mutants was rectified by NPS-2143. These findings demonstrate that CaSR-targeted compounds can rectify signaling disturbances caused by germline and somatic Gα11 mutations, which respectively lead to calcium disorders and tumorigenesis; and that ADH2-causing Gα11 mutatio
Jonas KC, Huhtaniemi I, Hanyaloglu AC, 2016, Single-molecule resolution of G protein-coupled receptor (GPCR) complexes, Editors: Shukla, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 55-72, ISBN: 978-0-12-803595-5
Jonas KC, Fanelli F, Huhtaniemi IT, et al., 2015, Single Molecule Analysis of Functionally Asymmetric G Protein-coupled Receptor (GPCR) Oligomers Reveals Diverse Spatial and Structural Assemblies, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 3875-3892, ISSN: 0021-9258
Psichas A, Sleeth ML, Murphy KG, et al., 2015, The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents, INTERNATIONAL JOURNAL OF OBESITY, Vol: 39, Pages: 424-429, ISSN: 0307-0565
Sposini S, Caltabiano G, Hanyaloglu AC, et al., 2015, Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers., Mol Cell Endocrinol, Vol: 399, Pages: 362-372
The chemokine prokineticin 2 (PK2) activates its cognate G protein-coupled receptor (GPCR) PKR2 to elicit various downstream signaling pathways involved in diverse biological processes. Many GPCRs undergo dimerization that can modulate a number of functions including membrane delivery and signal transduction. The aim of this study was to elucidate the interface of PKR2 protomers within dimers by analyzing the ability of PKR2 transmembrane (TM) deletion mutants to associate with wild type (WT) PKR2 in yeast using co-immunoprecipitation and mammalian cells using bioluminescence resonance energy transfer. Deletion of TMs 5-7 resulted in a lack of detectable association with WT PKR2, but could associate with a truncated mutant lacking TMs 6-7 (TM1-5). Interestingly, TM1-5 modulated the distance, or organization, between protomers and positively regulated Gαs signaling and surface expression of WT PKR2. We propose that PKR2 protomers form type II dimers involving TMs 4 and 5, with a role for TM5 in modulation of PKR2 function.
West C, Hanyaloglu AC, 2015, Minireview: Spatial Programming of G Protein-Coupled Receptor Activity: Decoding Signaling in Health and Disease., Mol Endocrinol, Vol: 29, Pages: 1095-1106
Probing the multiplicity of hormone signaling via G protein-coupled receptors (GPCRs) has demonstrated the complex signal pathways that underlie the multiple functions these receptors play in vivo. This is highly pertinent for the GPCRs key in reproduction and pregnancy that are exposed to cyclical and dynamic changes in their extracellular milieu. How such functional pleiotropy in GPCR signaling is translated to specific downstream cellular responses, however, is largely unknown. Emerging data strongly support mechanisms for a central role of receptor location in signal regulation via membrane trafficking. In this review, we discuss current progress in our understanding of the role membrane trafficking plays in location control of GPCR signaling, from organized plasma membrane signaling microdomains, potentially provided by both distinct endocytic and exocytic pathways, to more recent evidence for spatial control within the endomembrane system. Application of these emerging mechanisms in their relevance to GPCR activity in physiological and pathophysiological conditions will also be discussed, and in improving therapeutic strategies that exploits these mechanisms in order to program highly regulated and distinct signaling profiles.
Jean-Alphonse F, Bowersox S, Chen S, et al., 2014, Spatially Restricted G Protein-coupled Receptor Activity via Divergent Endocytic Compartments, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 3960-3977, ISSN: 0021-9258
Kandola MK, Sykes L, Lee YS, et al., 2014, EP2 Receptor Activates Dual G Protein Signaling Pathways that Mediate Contrasting Proinflammatory and Relaxatory Responses in Term Pregnant Human Myometrium, ENDOCRINOLOGY, Vol: 155, Pages: 605-617, ISSN: 0013-7227
Kim SH, Blanks A, Thornton S, et al., 2014, Oxytocin Receptor Antagonist, Atosiban, Drives Proinflammatory Effects in Human Amnion Via G(ai) Signaling., REPRODUCTIVE SCIENCES, Vol: 21, Pages: 111A-111A, ISSN: 1933-7191
Nikolopoulou E, Papacleovoulou G, Jean-Alphonse F, et al., 2014, Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential, JOURNAL OF LIPID RESEARCH, Vol: 55, Pages: 2479-2490, ISSN: 0022-2275
Jonas KC, Rivero-Mueller A, Huhtaniemi IT, et al., 2013, G Protein-Coupled Receptor Transactivation: From Molecules to Mice, RECEPTOR-RECEPTOR INTERACTIONS, Vol: 117, Pages: 433-450, ISSN: 0091-679X
Arulkumaran S, Kandola MK, Hoffman B, et al., 2012, The Roles of Prostaglandin EP 1 and 3 Receptors in the Control of Human Myometrial Contractility, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 97, Pages: 489-498, ISSN: 0021-972X
Al-Sabbagh M, Fusi L, Higham J, et al., 2011, NADPH Oxidase-Derived Reactive Oxygen Species Mediate Decidualization of Human Endometrial Stromal Cells in Response to Cyclic AMP Signaling, ENDOCRINOLOGY, Vol: 152, Pages: 730-740, ISSN: 0013-7227
Jean-Alphonse F, Hanyaloglu AC, 2011, Regulation of GPCR signal networks via membrane trafficking, MOLECULAR AND CELLULAR ENDOCRINOLOGY, Vol: 331, Pages: 205-214, ISSN: 0303-7207
Rivero-Muller A, Chou Y-Y, Ji I, et al., 2010, Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 2319-2324, ISSN: 0027-8424
Hanyaloglu AC, von Zastrow M, 2008, Regulation of GPCRs by Endocytic membrane trafficking and its potential implications, ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, Vol: 48, Pages: 537-568, ISSN: 0362-1642
N'Diaye E-N, Hanyaloglu AC, Kajihara KK, et al., 2008, The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-coupled receptor endocytosis, MOLECULAR BIOLOGY OF THE CELL, Vol: 19, Pages: 1252-1260, ISSN: 1059-1524
Hanyaloglu AC, von Zastrow M, 2007, A novel sorting sequence in the beta(2)-adrenergic receptor switches recycling from default to the Hrs-dependent mechanism, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 3095-3104, ISSN: 0021-9258
Hanyaloglu AC, McCullagh E, von Zastrow M, 2005, Essential role of Hrs in a recycling mechanism mediating functional resensitization of cell signaling, EMBO JOURNAL, Vol: 24, Pages: 2265-2283, ISSN: 0261-4189
Miles LEC, Hanyaloglu AC, Dromey JR, et al., 2004, Gonadotropin-releasing hormone receptor-mediated growth suppression of immortalized L beta T2 gonadotrope and stable HEK293 cell lines, ENDOCRINOLOGY, Vol: 145, Pages: 194-204, ISSN: 0013-7227
Ward BK, Magno AL, Davis EA, et al., 2004, Functional deletion of the calcium-sensing receptor in a case of neonatal severe hyperparathyroidism, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 89, Pages: 3721-3730, ISSN: 0021-972X
Eidne KA, Kroeger KM, Hanyaloglu AC, 2002, Applications of novel resonance energy transfer techniques to study dynamic hormone receptor interactions in living cells, TRENDS IN ENDOCRINOLOGY AND METABOLISM, Vol: 13, Pages: 415-421, ISSN: 1043-2760
Hanyaloglu AC, Seeber RM, Kohout TA, et al., 2002, Homo- and hetero-oligomerization of thyrotropin-releasing hormone (TRH) receptor subtypes - Differential regulation of beta-arrestins 1 and 2, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 277, Pages: 50422-50430, ISSN: 0021-9258
Hanyaloglu AC, Vrecl M, Kroeger KM, et al., 2001, Casein kinase II sites in the intracellular C-terminal domain of the thyrotropin-releasing hormone receptor and chimeric gonadotropin-releasing hormone receptors contribute to beta-arrestin-dependent internalization, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 276, Pages: 18066-18074, ISSN: 0021-9258
Kroeger KM, Hanyaloglu AC, Eidne KA, 2001, Applications of BRET to study dynamic G-protein coupled receptor interactions in living cells, 4th International Australian Peptide Conference, Publisher: KLUWER ACADEMIC PUBL, Pages: 155-162, ISSN: 0929-5666
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