Advances in the pharmacology of lGICs auxiliary subunits

Sex differences in central inflammatory pain sensitization are associated with differential expression of glycine receptors and GLP-1 at the spinal cord

“…On the other hand, our results showed that both males and females had increased auxiliary βGlyR expression. This subunit is unable to form a functional channel, however, it plays an important role in the modulation of the GlyRs currents [22]. In this respect, Bormann et al, described that heteropentameric GlyR composed by α and β subunits, expressed in spinal neurons, requires a higher glycine concentration to reach about 50% of maximal effect on receptor activation in comparison to homopentameric receptors, (EC 50 for αGlyR and αβGlyR is 30 and 54 μM, respectively) [23].…”

Glutamate Receptor

“…Nonfunctional receptors are retained intracellularly, suggesting that glutamate binding and associated conformational changes are prerequisites for the forward trafficking of intracellular iGluRs following multimeric assembly (Herguedas et al 2013). In addition to the pore-forming subunits, native iGluR protein complexes also contain auxiliary subunits and a wide variety of intracellular interaction partners (Traynelis et al 2010;Galaz et al 2015). Auxiliary subunits are defined by four key criteria: (1) they are not an integral component of the transduction pathway, (2) they are stably associated with pore-forming subunits, (3) they affect multiple aspects of receptor pharmacology, function and subcellular trafficking or targeting, (4) their co-assembly is required for proper neuronal functionality of the receptor (Galaz et al 2015;Howe 2015).…”

“…In addition to the pore-forming subunits, native iGluR protein complexes also contain auxiliary subunits and a wide variety of intracellular interaction partners (Traynelis et al 2010;Galaz et al 2015). Auxiliary subunits are defined by four key criteria: (1) they are not an integral component of the transduction pathway, (2) they are stably associated with pore-forming subunits, (3) they affect multiple aspects of receptor pharmacology, function and subcellular trafficking or targeting, (4) their co-assembly is required for proper neuronal functionality of the receptor (Galaz et al 2015;Howe 2015). In contrast, other interacting proteins are involved in transient and often dynamic interactions with iGluRs and they influence singular aspects of receptor function (e.g.…”

“…While previous studies raised the possibility that Neto1 and/or amyloid precursor protein (APP) are auxiliary subunits of NMDARs, further studies are necessary to confirm or discard these findings (Galaz et al 2015). Like other iGluRs, NMDARs also interact with a wide range of cytoskeletal, scaffolding and signaling proteins (e.g., α-actin-2, AP2, calmodulin, CaMKII, CARPI, COPII, GPS2, LIN7, LIN10, MAP1S, PACSIN1, plectin, PSD95, RACK1, SALM1, SAP97, SAP102, S-SCAM;Traynelis et al 2010;Collingridge et al 2013).…”

A Short Guide to Electrophysiology and Ion Channels

“…Each CLR subunit consists of a large N-terminal extracellular ligand binding domain and four transmembrane segments (TM1-4). The TM2 is involved in pore formation and TM3 and TM4 are connected by one large intracellular loop that is involved in various intracellular modulations (67,68). The CLR superfamily consists of nicotinic acetylcholine receptors (nAChR), γ-amino butyric acid A (GABAA), GABAA-ρ, glutamate-gated chloride receptor (GluCl), serotonin or 5-hydroxytryptamine (5 HT3), and glycine (GlyR) receptors.…”