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  - Balakrishnan, Ashwin
A1  - Hemmen, Katherina
A1  - Choudhury, Susobhan
A1  - Krohn, Jan-Hagen
A1  - Jansen, Kerstin
A1  - Friedrich, Mike
A1  - Beliu, Gerti
A1  - Sauer, Markus
A1  - Lohse, Martin J.
A1  - Heinze, Katrin G.
T1  - Unraveling the hidden temporal range of fast β2-adrenergic receptor mobility by time-resolved fluorescence
JF  - Communications Biology
N2  - G-protein-coupled receptors (GPCRs) are hypothesized to possess molecular mobility over a wide temporal range. Until now the temporal range has not been fully accessible due to the crucially limited temporal range of available methods. This in turn, may lead relevant dynamic constants to remain masked. Here, we expand this dynamic range by combining fluorescent techniques using a spot confocal setup. We decipher mobility constants of β\(_{2}\)-adrenergic receptor over a wide time range (nanosecond to second). Particularly, a translational mobility (10 µm\(^{2}\)/s), one order of magnitude faster than membrane associated lateral mobility that explains membrane protein turnover and suggests a wider picture of the GPCR availability on the plasma membrane. And a so far elusive rotational mobility (1-200 µs) which depicts a previously overlooked dynamic component that, despite all complexity, behaves largely as predicted by the Saffman-Delbrück model.
KW  - G-protein-coupled receptors
KW  - molecular mobility
KW  - temporal range
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301140
VL  - 5
IS  - 1
ER  -