title: Modulation of mouse rod photoreceptor responses by Grb14 protein.
abstract: Previous experiments have indicated that growth factor receptor-bound protein 14 (Grb14) may modulate rod photoreceptor cGMP-gated channels by decreasing channel affinity for cGMP; however, the function of Grb14 in rod physiology is not known. In this study, we examined the role of Grb14 by recording electrical responses from rods in which the gene for the Grb14 protein had been deleted. Suction-electrode recordings from single mouse rods showed that responses of dark-adapted Grb14(-/-) mice to brief flashes decayed more rapidly than strain-controlled wild type (WT) rods, with decreased values of both integration time and the exponential time course of decay (τREC). This result is consistent with an increase in channel affinity for cGMP produced by deletion of Grb14. However, Grb14(-/-) mouse rods also showed little change in dark current and a large and significant decrease in the limiting time constant τD, which are not consistent with an effect on channel affinity but seem rather to indicate modulation of the rate of inactivation of cyclic nucleotide phosphodiesterase 6 (PDE6). Grb14 has been reported to translocate from the inner to the outer segment in bright light, but we saw effects on response time course even in dark-adapted rods, although the effects were somewhat greater after rods had been adapted by exposure to bleaching illumination. Our results indicate that the mechanism of Grb14 action may be more complex than previously realized.
authors.affiliation: From the Department of Integrative Biology and Physiology, UCLA, Los Angeles, California 90095-7239.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Woodruff
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Fain
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics / Q000378:metabolism; D003623:Dark Adaptation / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; C490977:Grb14 protein, mouse; D011506:Proteins; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D006152:Cyclic GMP
keywords: Cyclic GMP (cGMP); Cyclic Nucleotides; Neurobiology; Photoreceptors; Receptor-tyrosine Kinase; Retina