GNAT1-GTP hydrolyses its bound GTP to GDP

Stable Identifier
R-HSA-2584246
Type
Reaction [transition]
Species
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
10051575 The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit.

Makino, ER, Handy, JW, Li, T, Arshavsky, VY

Proc Natl Acad Sci U S A 1999
19818506 Novel mutations and electrophysiologic findings in RGS9- and R9AP-associated retinal dysfunction (Bradyopsia)

Michaelides, M, Li, Z, Rana, NA, Richardson, EC, Hykin, PG, Moore, AT, Holder, GE, Webster, AR

Ophthalmology 2010
16908407 RGS expression rate-limits recovery of rod photoresponses

Krispel, CM, Chen, D, Melling, N, Chen, YJ, Martemyanov, KA, Quillinan, N, Arshavsky, VY, Wensel, TG, Chen, CK, Burns, ME

Neuron 2006
14702087 Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation

Nishiguchi, KM, Sandberg, MA, Kooijman, AC, Martemyanov, KA, Pott, JW, Hagstrom, SA, Arshavsky, VY, Berson, EL, Dryja, TP

Nature 2004
10564809 Structure, alternative splicing, and expression of the human RGS9 gene

Zhang, K, Howes, KA, He, W, Bronson, JD, Pettenati, MJ, Chen, C, Palczewski, K, Wensel, TG, Baehr, W

Gene 1999
9459445 RGS9, a GTPase accelerator for phototransduction.

He, W, Cowan, CW, Wensel, TG

Neuron 1998
10676965 Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1

Chen, CK, Burns, ME, He, W, Wensel, TG, Baylor, DA, Simon, MI

Nature 2000
12119397 R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1

Hu, G, Wensel, TG

Proc. Natl. Acad. Sci. U.S.A. 2002
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Catalyst Activity
Title
GTPase activity of GNAT1-GTP:PDE6 [photoreceptor disc membrane]
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