Kinetic fingerprinting of metabotropic glutamate receptors

Taulant Kukaj; Christian Sattler; Thomas Zimmer; Ralf Schmauder; Klaus Benndorf

doi:10.1038/s42003-023-04468-z

Kinetic fingerprinting of metabotropic glutamate receptors

Commun Biol. 2023 Jan 27;6(1):104. doi: 10.1038/s42003-023-04468-z.

Authors

Taulant Kukaj¹, Christian Sattler¹, Thomas Zimmer¹, Ralf Schmauder¹, Klaus Benndorf²

Affiliations

¹ Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743, Jena, Germany.
² Institute of Physiology II, Jena University Hospital, Friedrich Schiller University Jena, 07743, Jena, Germany. Klaus.benndorf@med.uni-jena.de.

Abstract

Dimeric metabotropic glutamate receptors (mGluRs) are abundantly expressed in neurons. In mammals, eight subunit isoforms, mGluR1-8, have been identified, forming the groups I, II, and III. We investigated receptor dimerization and kinetics of these mGluR isoforms in excised membrane patches by FRET and confocal patch-clamp fluorometry. We show that 5 out of 8 homodimeric receptors develop characteristic glutamate-induced on- and off-kinetics, as do 11 out of 28 heterodimers. Glutamate-responsive heterodimers were identified within each group, between groups I and II as well as between groups II and III, but not between groups I and III. The glutamate-responsive heterodimers showed heterogeneous activation and deactivation kinetics. Interestingly, mGluR7, not generating a kinetic response in homodimers, showed fast on-kinetics in mGluR2/7 and mGluR3/7 while off-kinetics retained the speed of mGluR2 or mGluR3 respectively. In conclusion, glutamate-induced conformational changes in heterodimers appear within each group and between groups if one group II subunit is present.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Glutamic Acid
Kinetics
Mammals
Neurons
Receptors, Metabotropic Glutamate*

Substances

Glutamic Acid
Receptors, Metabotropic Glutamate