Sustained Activity of Metabotropic Glutamate Receptor: Homer, Arrestin, and Beyond

Abstract EN

When activated, metabotropic glutamate receptors (mGlus) exert long-lasting changes within the glutamatergic synapses.

One mechanism is a tonic effect of downstream signal transduction pathways via sustained activation of mGlu itself.

Like many other G protein-coupled receptors (GPCRs), mGlu can exist in a constitutively active state, which persists agonist independently.

In this paper, we review the current knowledge of the mechanisms underlying the constitutive activity of group I mGlus.

The issues concerning Homer1a mechanism in the constitutive activity of group I mGlus and recent findings regarding the significant role of β-arrestin in sustained GPCR activity are also discussed.

We propose that once in a state of sustained activation, the mGlu persistently activates downstream signaling pathways, including various adaptor proteins and kinases, such as β-arrestin and mitogen-activated protein kinases.

In turn, these effector molecules bind to or phosphorylate the mGlu C-terminal binding domains and consequently regulate the activation state of the mGlu.