Ultrastructural localization of retinal guanylate cyclase in human and monkey retinas

Liu, Xinran; Seno, Keiji; Hayashi, Fumio; Yamazaki, Akio; Matsumoto, Hiroyuki; Wakabayashi, Takashi; Usukura, Jiro

doi:10.1006/exer.1994.1162

Cited by 130 publications

(100 citation statements)

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“…However, in this genotype, we consistently observed uneven labeling of GC1 throughout the POS with accumulation in areas closer to the IS. Some of these findings have been reported previously (30,(32)(33)(34), and we have included them here for comparison.…”

Section: Protein Expression Patterns In Wt Gc1mentioning

confidence: 62%

Impaired Association of Retinal Degeneration-3 with Guanylate Cyclase-1 and Guanylate Cyclase-activating Protein-1 Leads to Leber Congenital Amaurosis-1

Zulliger

Naash

Rajala

et al. 2015

Journal of Biological Chemistry

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Background: Defects in the function of guanylate cyclase 1 (GC1) cause Leber congenital amaurosis (LCA) type 1. Results: GC1, GCAP1, and RD3 form a complex in the endoplasmic reticulum that targets GC1 to outer segments. Conclusion: A subset of LCA1 is caused by impaired formation of the RD3-GC1-GCAP1 complex. Significance: Understanding the molecular interaction of RD3 with GC1 and GCAP1 has potential therapeutic benefits for LCA1.

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Section: Protein Expression Patterns In Wt Gc1mentioning

confidence: 62%

Impaired Association of Retinal Degeneration-3 with Guanylate Cyclase-1 and Guanylate Cyclase-activating Protein-1 Leads to Leber Congenital Amaurosis-1

Zulliger

Naash

Rajala

et al. 2015

Journal of Biological Chemistry

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“…Retinal guanylate cyclase was also shown to concentrate at the marginal region of the disc membrane (35). Thus, the two enzymes controlling cGMP levels, PDE6 and guanylate cyclase, and the plasma membrane cGMP-gated channel might be localized in close proximity.…”

Section: Discussionmentioning

confidence: 97%

Characterization of Human Cone Phosphodiesterase-6 Ectopically Expressed in Xenopus laevis Rods

Muradov

Boyd

Haeri

et al. 2009

Journal of Biological Chemistry

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PDE6 (phosphodiesterase-6) is the effector molecule in the vertebrate phototransduction cascade. Progress in understanding the structure and function of PDE6 has been hindered by lack of an expression system of the enzyme. Here we report ectopic expression and analysis of compartmentalization and membrane dynamics of the enhanced green fluorescent protein (EGFP) fusion protein of human cone PDE6C in rods of transgenic Xenopus laevis. EGFP-PDE6C is correctly targeted to the rod outer segments in transgenic Xenopus, where it displayed a characteristic striated pattern of EGFP fluorescence. Immunofluorescence labeling indicated significant and light-independent co-localization of EGFP-PDE6C with the disc rim marker peripherin-2 and endogenous frog PDE6. The diffusion of EGFP-PDE6C on disc membranes investigated with fluorescence recovery after photobleaching was markedly slower than theoretically predicted. The enzymatic characteristics of immunoprecipitated recombinant PDE6C were similar to known properties of the native bovine PDE6C. PDE6C was potently inhibited by the cone-and rod-specific PDE6 ␥-subunits. Thus, transgenic Xenopus laevis is a unique expression system for PDE6 well suited for analysis of the mechanisms of visual diseases linked to PDE6 mutations.Phosphodiesterases of cyclic nucleotides (PDEs) 2 are essential enzymes controlling cellular levels of cAMP and cGMP. Eleven families of PDEs have been identified in mammals on the grounds of sequence homology, substrate selectivity, and regulation (1). Photoreceptor-specific PDEs in rods and cones comprise the sixth PDE family (PDE6) and serve as the effector enzymes in the vertebrate phototransduction cascade (1-5). Rod PDE6 is composed of homologous catalytic ␣-subunit (PDE6A) and ␤-subunit (PDE6B) and two copies of a small inhibitory ␥-subunit (P␥) (3). Cone PDE6 is a catalytic dimer of two identical ␣Ј-subunits (PDE6C) (3). A cone-specific inhibitory P␥-subunit is highly homologous to the rod P␥ (6). In rod photoreceptors, PDE6 is located in the specialized compartments called rod outer segments (ROS), where it associates with disc membranes. The membrane attachment of PDE6 is mediated by farnesylation of the PDE6A C terminus and geranylgeranylation of the PDE6B C terminus (7). In cones, geranylgeranylated PDE6C resides on infoldings of the cone outer segment plasma membrane (8). Following photoexcitation of rod or cone photoreceptor cells, PDE6 is activated by the GTPbound transducin ␣-subunit (G␣ t GTP) that relieves the P␥ inhibition of the enzyme. cGMP hydrolysis by active PDE6 leads to a cellular response due to a closure of cGMP-gated channels in the photoreceptor plasma membrane (2-5).Although PDE6 plays a prominent role in vertebrate vision, the structure-function relationships of PDE6 are poorly understood in comparison with other key phototransduction proteins. The lack of an expression system for PDE6 has become a major impediment for PDE6 research. Importantly, an expression system for PDE6 is required to elucidate the mechanisms of visua...

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“…Alternatively, GCAP1 may play a role in unidentified pathways at the cone synapse. In wild-type mice, both GCAP1 and GC1 are found in photoreceptor terminals and could modulate cGMP channels at the synapse (8,26,33,34). G1T3 ϩ GCAP Ϫ/Ϫ mice exhibit high levels of GCAP1 in the cone somata and pedicles (Fig.…”

Section: Discussionmentioning

confidence: 99%

Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice

Pennesi

Howes

Baehr

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Mediated by guanylate cyclase-activating proteins (GCAPs), cytoplasmic Ca 2؉ levels regulate the activity of photoreceptor guanylate cyclase (GC) and the synthesis of cGMP, the internal transmitter of phototransduction. When GCAP1 is expressed in transgenic mice on a GCAP null background, it restores the wild-type flash responses in rod photoreceptors. In this communication, we explored the role of GCAP1 in cone photoreceptors by using electroretinograms (ERGs). Under cone isolation conditions, ERGs recorded from mice lacking both GCAP1 and GCAP2 had normal amplitudes of the saturated a-wave and b-wave. However, recordings from these mice demonstrated a widened b-wave and increased sensitivity of both M-and UV-cone systems. Paired-flash ERGs revealed a delayed recovery of both the cone driven b-wave and a-wave and suggest that the delay originated from the photoreceptors. To test whether GCAP1 could restore normal cone response recovery, mice that expressed only transgenic GCAP1 in the absence of wild-type GCAP expression were tested. Immunohistochemical analysis demonstrated that cones of these mice expressed high levels of GCAP1. Paired-flash ERGs showed that the recovery of the cone-driven a-wave was restored to normal, whereas recovery of the cone-driven b-wave was slightly faster than that observed in wild-type mice. These studies reveal that, similar to rods, deletion of GCAP1 and GCAP2 delays the recovery of light responses in cones and GCAP1 restores the recovery of cone responses in the absence of GCAP2.

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Ultrastructural localization of retinal guanylate cyclase in human and monkey retinas

Cited by 130 publications

References 0 publications

Impaired Association of Retinal Degeneration-3 with Guanylate Cyclase-1 and Guanylate Cyclase-activating Protein-1 Leads to Leber Congenital Amaurosis-1

Impaired Association of Retinal Degeneration-3 with Guanylate Cyclase-1 and Guanylate Cyclase-activating Protein-1 Leads to Leber Congenital Amaurosis-1

Characterization of Human Cone Phosphodiesterase-6 Ectopically Expressed in Xenopus laevis Rods

Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice

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