The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors.
ABSTRACT Retinal guanylate cyclases 1 and 2 (GC1 and GC2) are responsible for synthesis of cyclic GMP in rods and cones, but their individual contributions to phototransduction are unknown. We report here that the deletion of both GC1 and GC2 rendered rod and cone photoreceptors nonfunctional and unstable. In the rod outer segments of GC double knock-out mice, guanylate cyclase-activating proteins 1 and 2, and cyclic GMP phosphodiesterase were undetectable, although rhodopsin and transducin alpha-subunit were mostly unaffected. Outer segment membranes of GC1-/- and GC double knock-out cones were destabilized and devoid of cone transducin (alpha- and gamma-subunits), cone phosphodiesterase, and G protein-coupled receptor kinase 1, whereas cone pigments were present at reduced levels. Real time reverse transcription-PCR analyses demonstrated normal RNA transcript levels for the down-regulated proteins, indicating that down-regulation is posttranslational. We interpret these results to demonstrate an intrinsic requirement of GCs for stability and/or transport of a set of membrane-associated phototransduction proteins.
Article: Three kinds of guanylate cyclase expressed in medaka photoreceptor cells in both retina and pineal organ.[show abstract] [hide abstract]
ABSTRACT: Three kinds of cDNAs encoding the putative photoreceptor-specific guanylate cyclases (GCs), OlGC-R1, OlGC-R2, and OlGC-C, were isolated from a retinal cDNA library of the medaka, Oryzias latipes. The deduced amino acid sequences of OlGC-R1 and -C are closely related but slightly different from those of OlGC4 and OlGC5, respectively. In situ hybridization locates the mRNA of both OlGC-R1 and -R2 in rods, and OlGC-C mRNA is found in all four types of cone cells. It is likely that medaka rods and cones produce distinct GC subtypes and that two kinds of photoreceptor-specific GCs are coexpressed in rods. Also, hybridization signals are detected in the pineal organ, suggesting that OlGC-R1 and -C contribute also to phototransduction in pinealocytes.Biochemical and Biophysical Research Communications 03/1999; 255(2):216-20. · 2.48 Impact Factor
Article: Lymphocytic hypophysitis and infundibuloneurohypophysitis; clinical and pathological evaluations.[show abstract] [hide abstract]
ABSTRACT: This report describes the clinical and pathological characteristics of two patients with lymphocytic hypophysitis (LHy) and two with infundibuloneurohypophysitis (INHy). Two of the patients were women and two were men, and their ages were between 27 and 38 years old. This disease was not associated with either pregnancy or the postpartum period in the female patients. Two of the patients presented with diabetes insipidus, one with panhypopituitarism and right abducens paralysis and one with headache and galactorrhea. At presentation three of the patients had mild to moderate hyperprolactinemia and one had low prolactin levels. All four had abnormal magnetic resonance imaging (MRI): focal nodular enlarging of the infundibulum and normal hypophysis in one, expanding sellar masses in two, and diffusely thickened stalk with slightly enlarged pituitary gland in one. Three cases showed no sign of adenohypophysial deficiency with stimulation tests. One patient had associated chronic lymphocytic thyroiditis. Of the first three patients, one patient underwent transcranial and two underwent transnasal transsphenoidal (TNTS) surgery for mass excisions since they were thought to have pituitary tumors. Endoscopic endonasal transsphenoidal biopsy was performed in the last one with a suspicion of LHy. The pathological and immunohistochemical examinations revealed lymphocytic infiltration. Hyperprolactinemia resolved with surgery in two patients and one developed diabetes insipidus as a complication. We conclude that LHy and infundibuloneurohypophysitis should be considered in the differential diagnosis of the mass lesions of the sellar region and also should be kept in the mind for the etiopathogenesis of cases of hyperprolactinemia, galactorrhea and diabetes insipidus. In suspected cases endoscopic endonasal biopsy for the histopathological diagnosis can be a safe approach.Endocrine Journal 09/1999; 46(4):505-12. · 2.03 Impact Factor
Article: Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse.[show abstract] [hide abstract]
ABSTRACT: Retinal degeneration in the mouse mutant, rd, was previously shown to be a disorder of cyclic nucleotide metabolism involving a deficiency in the activity of the rod photoreceptor cGMP phosphodiesterase (PDE). We have characterized the normal and rd PDE beta-subunit gene, and their respective transcripts, by PCR and direct sequence analysis. We show that the gene consists of at least 22 exons ranging in size from 48 base pairs to several hundred base pairs, covering greater than 25 kilobases. Within a 67-base-pair exon of the rd PDE beta-subunit gene, we identified a nonsense ochre mutation (a C----A transversion in codon 347) that truncates the normal gene product, eliminating more than one-half of the peptide chain, including the putative catalytic domain. The consequences of the truncation are consistent with the observed phenotypes in rd mice heterozygous and homozygous for the disorder. The nonsense mutation was also found in another related and in six unrelated strains displaying the rd phenotype, indicating that the rd allele arose from a single genetic event. The results strongly argue for the nonsense mutation being responsible for retinal degeneration in the rd mouse.Proceedings of the National Academy of Sciences 11/1991; 88(19):8322-6. · 9.68 Impact Factor