TY  - JOUR
A1  - Liu, Ruiqi
A1  - Friedrich, Mike
A1  - Hemmen, Katherina
A1  - Jansen, Kerstin
A1  - Adolfi, Mateus C.
A1  - Schartl, Manfred
A1  - Heinze, Katrin G.
T1  - Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism
JF  - Frontiers in Endocrinology
N2  - 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, 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.
KW  - fluorescence lifetime imaging microscopy
KW  - Förster Resonance Energy Transfer
KW  - Mc4r
KW  - puberty
KW  - Xiphophorus
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354261
SN  - 1664-2392
VL  - 14
ER  - 
TY  - JOUR
A1  - Liu, Ruiqi
A1  - Kinoshita, Masato
A1  - Adolfi, Mateus C.
A1  - Schartl, Manfred
T1  - Analysis of the role of the Mc4r system in development, growth, and puberty of medaka
JF  - Frontiers in Endocrinology
N2  - In mammals the melanocortin 4 receptor (Mc4r) signaling system has been mainly associated with the regulation of appetite and energy homeostasis. In fish of the genus Xiphophorus (platyfish and swordtails) puberty onset is genetically determined by a single locus, which encodes the mc4r. Wild populations of Xiphophorus are polymorphic for early and late-maturing individuals. Copy number variation of different mc4r alleles is responsible for the difference in puberty onset. To answer whether this is a special adaptation of the Mc4r signaling system in the lineage of Xiphophorus or a more widely conserved mechanism in teleosts, we studied the role of Mc4r in reproductive biology of medaka (Oryzias latipes), a close relative to Xiphophorus and a well-established model to study gonadal development. To understand the potential role of Mc4r in medaka, we characterized the major features of the Mc4r signaling system (mc4r, mrap2, pomc, agrp1). In medaka, all these genes are expressed before hatching. In adults, they are mainly expressed in the brain. The transcript of the receptor accessory protein mrap2 co-localizes with mc4r in the hypothalamus in adult brains indicating a conserved function of modulating Mc4r signaling. Comparing growth and puberty between wild-type and mc4r knockout medaka revealed that absence of Mc4r does not change puberty timing but significantly delays hatching. Embryonic development of knockout animals is retarded compared to wild-types. In conclusion, the Mc4r system in medaka is involved in regulation of growth rather than puberty.
KW  - medaka
KW  - Mc4r
KW  - knockout
KW  - puberty
KW  - growth
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201472
VL  - 10
ER  -