Meta-Biol

• Pathways

Active Gt alpha (GNAT-GTP) can be inactivated by a slow, intrinsic GTPase activity that hydrolyses GTP to GDP. Once GNAT1 has GDP bound, it no longer binds to the gamma subunit of PDE6 (PDE6-gamma) that then resumes inhibition of the catalytic subunit of PDE6. The hydrolysis of GTP is accelerated by a GAP (GTPase accelerating protein) complex that consists of Regulator of G protein signaling 9 (RGS9-1, RGS9 isoform 3) (He et al. 1998, Zhang et al. 1999), Guanine nucleotide binding protein subunit beta 5, long form (GNB5) (Makino et al. 1999) and RGS9 anchoring protein (RGS9BP, aka R9AP) (Hu & Wensel 1998). The affinity of GNAT GTP for the GAP complex is relatively low, but is increased significantly by the presence of PDE-gamma. Shutoff of Gt is the rate-limiting step in the recovery of the single photon response of rods (Chen et al. 2000, Krispel et al. 2006). Persons with defective GAP experience bradyopsia or "slow vision" in which there are difficulties in adjusting to changes in brightness and to tracking moving objects (Michaelides et al. 2010, Nishiguchi et al. 2004).