Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-354261
- Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, theXiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.…
Autor(en): | Ruiqi Liu, Mike Friedrich, Katherina Hemmen, Kerstin Jansen, Mateus C. Adolfi, Manfred Schartl, Katrin G. Heinze |
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URN: | urn:nbn:de:bvb:20-opus-354261 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Frontiers in Endocrinology |
ISSN: | 1664-2392 |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 14 |
Aufsatznummer: | 1267590 |
Originalveröffentlichung / Quelle: | Frontiers in Endocrinology (2023) 14:1267590. https://doi.org/10.3389/fendo.2023.1267590 |
DOI: | https://doi.org/10.3389/fendo.2023.1267590 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Förster Resonance Energy Transfer; Mc4r; Xiphophorus; fluorescence lifetime imaging microscopy; puberty |
Datum der Freischaltung: | 10.05.2024 |
Datum der Erstveröffentlichung: | 10.11.2023 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |