title: Loss of the effector function in a transducin-alpha mutant associated with Nougaret night blindness.
abstract: A missense mutation, G38D, was found in the rod transducin alpha subunit (Galpha(t)) in individuals with the Nougaret form of dominant stationary night blindness. To elucidate the mechanism of Nougaret night blindness, we have examined the key functional properties of the mutant transducin. Our data show that the G38D mutation does not alter the interaction between Galpha(t) and Gbetagamma(t) or activation of transducin by photoexcited rhodopsin (R*). The mutant Galpha(t) has only a modestly (approximately 2.5-fold) reduced k(cat) value for GTP hydrolysis. The GTPase activity of Galpha(t)G38D can be accelerated by photoreceptor regulator of G protein signaling, RGS9. Analysis of the Galpha(t)G38D interaction with cGMP phosphodiesterase revealed marked impairment of the mutant effector function. Galpha(t)G38D completely fails to bind the inhibitory PDE gamma subunit and activate the enzyme. Altogether, our results demonstrate a novel molecular mechanism in dominant stationary night blindness. In contrast to known forms of the disease caused by constitutive activation of the visual cascade, the Nougaret form has its origin in attenuated visual signaling due to loss of effector function by transducin G38D mutant.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Muradov
authors.forename: N O
authors.initials: NO
authors.lastname: Artemyev
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009755:Night Blindness / Q000209:etiology*; D015293:Transducin / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014357:Trypsin; D020558:GTP Phosphohydrolases; D015293:Transducin