Open AccessSerotonin receptor oligomerization regulates cAMP-based signaling
Author(s) -
Sonal Prasad,
Evgeni Ponimaskin,
André Zeug
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.230334
Subject(s) - förster resonance energy transfer , serotonergic , receptor , biology , 5 ht receptor , microbiology and biotechnology , serotonin , biophysics , signal transduction , endogeny , g protein coupled receptor , intracellular , neuroscience , endocrinology , biochemistry , fluorescence , physics , quantum mechanics
Protein-protein interaction is often investigated using quantitative molecular microscopy with Förster Resonant Energy Transfer (FRET). We combined ‘linear unmixing FRET’ (lux-FRET) with the simultaneous application of a FRET-based biosensor for cAMP to investigate the oligomerization between the 5-HT7 receptor (5-HT7R) and the 5-HT1A receptor (5-HT1AR) and its importance for cAMP signaling. We found that the 5-HT7R not only stimulates cAMP production, but also forms hetero-oligomers with 5-HT1AR, which blocks the inhibitory effect of the latter. 5-HT7R signaling however is not affected by this hetero-oligomerization. By modeling the kinetics of intracellular cAMP level changes in relation to the 5-HT7R:5-HT1AR stoichiometry we were able to decipher the complex signaling characteristics of endogenous serotonin receptors in cultured hippocampal neurons. Our findings indicate that the serotonergic signaling is not only modulated by the concentration of an individual receptor but also by its specific interaction with other receptors in endogenous systems. We conclude that the regulated ratio of serotonin receptors in immature and mature neurons may be critically involved in both the onset and response to treatments of psychiatric diseases such as anxiety and depression.