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  - 
TY  - JOUR
A1  - Klenk, Christoph
A1  - Hommers, Leif
A1  - Lohse, Martin J.
T1  - Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone 1 receptor
JF  - Frontiers in Endocrinology
N2  - Parathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to G\(_s\) and increased activation of G\(_q\) compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling.
KW  - GPCRs
KW  - parathyroid hormone 1 receptor
KW  - matrix metalloproteinase
KW  - ectodomain cleavage
KW  - biased signaling
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262055
SN  - 1664-2392
VL  - 13
ER  -