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Loss of the Effector Function in a Transducin-α Mutant Associated with Nougaret Night Blindness
Journal article   Open access   Peer reviewed

Loss of the Effector Function in a Transducin-α Mutant Associated with Nougaret Night Blindness

Khakim G Muradov and Nikolai O Artemyev
The Journal of biological chemistry, Vol.275(10), pp.6969-6974
03/10/2000
DOI: 10.1074/jbc.275.10.6969
PMID: 10702259
url
https://doi.org/10.1074/jbc.275.10.6969View
Published (Version of record) Open Access

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.

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