8.A.16.2.6
Voltage dependent Ca²⁺ channel γ8 subunit, CACNG8 or TARP γ8, of 425 aas and 4 or 5 TMSs. It interacts with calcineurin to regulate AMPA receptor phosphorylation and trafficking (Itakura et al. 2014). It regulates the activity of L-type calcium channels that contain CACNA1C as the pore-forming subunit (Shi et al. 2010). It also regulates the gating properties of AMPARs while promoting their targeting to the cell membrane and synapses and modulating their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization (Kato et al. 2010). It does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. TARP gamma8 is predominantly expressed in the forebrain and is enriched in the hippocampus, a region associated with temporal lobe epilepsy, and may allow development of refined AMPAR epilepsy therapeutics (Dohrke et al. 2020). SNP rs10420324 in the AMPA receptor auxiliary subunit TARP gamma-8 regulates the susceptibility to antisocial personality disorder (Peng et al. 2021). The TARP gamma8-selective negative allosteric modulator JNJ-55511118 influences AMPA receptor gating and channel conductance (Coombs et al. 2022). TARP gamma-8 regulates the AMPAR which mediates various brain functions including learning and memory, and it has been imaged (Yu et al. 2022). A deficiency of transmembrane AMPA receptor regulatory protein gamma-8 leads to attention-deficit hyperactivity disorder-like behavior in mice (Bai et al. 2022). Negative modulation of AMPA receptors bound to transmembrane AMPA receptor regulatory protein gamma-8 blunts the positive reinforcing properties of alcohol and sucrose in a brain region-dependent manner in male mice (Hoffman et al. 2023). It is an AMPA receptor regulatory protein (TARP gamma-8) in the brain (Yamasaki et al. 2023).