The interaction between mGluR1 and the calcium channel Cav₂.₁ preserves coupling in the presence of long Homer proteins.
Group I metabotropic glutamate receptors (mGluR1 and 5) are G protein coupled receptors that regulate neuronal activity in a number of ways. Some of the most well studied functions of group I mGluRs, such as initiation of multiple forms of mGluR-dependent long-term depression, require receptor localization near the post-synaptic density (PSD). This localization is in turn dependent on the Homer family of scaffolding proteins which bind to a small motif on the distal C-termini of mGluR1 and 5, localize the receptors near the PSD, strengthen coupling to post-synaptic effectors and simultaneously uncouple the mGluRs from extra-synaptic effectors such as voltage dependent ion channels. Here the selectivity of this uncoupling process was examined by testing the ability of Homer-2b to uncouple mGluR1 from multiple voltage dependent calcium channels including Ca(V2.2) (N-type), Ca(V3.2) (T-type), and Ca(V2.1) (P/Q-type) expressed in rat sympathetic neurons from the superior cervical ganglion (SCG). Of these, only the mGluR1-Ca(V2.1) modulatory pathway was insensitive to Homer-2b expression. Uncoupling from this channel was achieved by co-expression of an mGluR1 C-terminal protein designed to disrupt a previously described direct interaction between these two proteins, suggesting that this interaction allows incorporation of Ca(V2.1) into the mGluR1/Homer signaling complex, thereby preserving modulation in the presence of scaffolding Homer proteins. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
University of Rochester Medical Center, Department of Pharmacology and Physiology, Rochester, NY 14642, USA.
Donald
D
Beqollari
Paul J
PJ
Kammermeier
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000096:biosynthesis / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1