Mutations in the Gene for the B-Subunit of Rod Photoreceptor Cgmp-Specific Phosphodiesterase (PDEB) in Patients with Retinal Dystrophies and Dysfunctions

Veske, Andres; Orth, Ulrike; Rüther, Klaus; Zrenner, Eberhart; Rosenberg, Thomas; Baehr, Wolfgang; Gal, Andreas

doi:10.1007/978-1-4615-1897-6_35

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…There are numerous precedents for forms of stationary night blindness (a group of nondegenerative retinal diseases) and forms of progressive night blindness (i.e., retinitis pigmentosa) being due to allelic defects at the same genetic loci. As examples, distinct mutations of the genes encoding two other members of the rod phototransduction pathway, rhodopsin and the β subunit of rod cGMPphosphodiesterase, have been found to cause either stationary night blindness or retinitis pigmentosa (Dryja and Li, 1995 ;Dryja et al, 1993 ;Sieving et al, 1995 ;McLaughlin et al, 1993 ;McLaughlin et al, 1995 ;Seminago et al, 1995 ;Danciger et al, 1995 ;Valverde et al, 1996 ;Veske et al, 1995 ;Gal et al, 1994). In addition, two loci responsible for X-linked stationary night blindness are closely linked to chromosomal regions containing X-linked retinitis pigmentosa genes (Musarella et al, 1989 ;Gal et al, 1989 ;Bergen et al, 1996) and may be allelic with them.…”

Section: Introductionmentioning

confidence: 97%

Evaluation of the Rhodopsin Kinase Gene in Patients with Retinitis Pigmentosa

Yamamoto

Khani

Berson

et al. 1997

Experimental Eye Research

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Section: Introductionmentioning

confidence: 97%

Evaluation of the Rhodopsin Kinase Gene in Patients with Retinitis Pigmentosa

Yamamoto

Khani

Berson

et al. 1997

Experimental Eye Research

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“…Lack of functional PDE6 in the rod OS leads to elevation of cGMP levels and causes rapid retinal degeneration (RD) in animal models and humans (Farber and Lolley, 1974, Bowes et al, 1990, Pittler and Baehr, 1991, Liu et al, 2004, Ramamurthy et al, 2004). The possibility that abnormal PDE6 trafficking may underlie RP is highlighted by the PDE6B mutation L854V in the protein C-terminal CAAX motif (Veske et al, 1995). Isoprenylation modifications of PDE6 are critical to the PDE6 interaction with membranes and transport (Anant et al, 1992, Catty et al, 1992, Veske et al, 1995, Karan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…The possibility that abnormal PDE6 trafficking may underlie RP is highlighted by the PDE6B mutation L854V in the protein C-terminal CAAX motif (Veske et al, 1995). Isoprenylation modifications of PDE6 are critical to the PDE6 interaction with membranes and transport (Anant et al, 1992, Catty et al, 1992, Veske et al, 1995, Karan et al, 2008). The C-terminal CAAX boxes of mammalian PDE6A and PDE6B specify farnesylation and geranylgeranylation, respectively (Anant et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia

Cheguru

Majumder

Artemyev

2015

Molecular and Cellular Neuroscience

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Phosphodiesterases-6 (PDE6) are essential effector enzymes in vertebrate photoreceptor cells. Mutations in rod and cone PDE6 cause recessive retinitis pigmentosa and achromatopsia, respectively. The mechanisms of missense PDE6 mutations underlying severe visual disorders are poorly understood. To probe these mechanisms, we expressed seven known missense mutants of cone PDE6C in rods of transgenic X. laevis and examined their stability and compartmentalization. PDE6C proteins with mutations in the catalytic domain, H602L and E790K, displayed modestly reduced proteolytic stability, but they were properly targeted to the outer segment of photoreceptor cells. Mutations in the regulatory GAF domains, R104W, Y323N, and P391L led to a proteolytic degradation of the proteins involving a cleavage in the GAFb domain. Lastly, the R29W and M455V mutations residing outside the conserved PDE6 domains produced a pattern of subcellular compartmentalization different from that of PDE6C. Thus, our results suggest a spectrum of mechanisms of missense PDE6C mutations in achromatopsia including catalytic defects, protein mislocalization, or a specific sequence of proteolytic degradation.

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“…1, L854V in protein PDE6B, is known as a cause of Retinitis Pigmentosa 40 (RP40). 65 It maps into the non-globular segment (840-854) responsible for S-geranylgeranylation. This mutation is predicted by the published PrePS webserver 54 to alter an S-geranylgeranyl PTM motif by switching its speci¯city to S-farnesylation instead (the corresponding interactive cartoon can be found on the HPMV website as both a web page link and a downloadable jar¯le).…”

Section: Hpmv Application: Variant L854v In Protein Pde6bmentioning

confidence: 99%

HPMV: Human protein mutation viewer — relating sequence mutations to protein sequence architecture and function changes

Sherman

Kuchibhatla

Limviphuvadh

et al. 2015

J. Bioinform. Comput. Biol.

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Next-generation sequencing advances are rapidly expanding the number of human mutations to be analyzed for causative roles in genetic disorders. Our Human Protein Mutation Viewer (HPMV) is intended to explore the biomolecular mechanistic signi¯cance of non-synonymous human mutations in protein-coding genomic regions. The tool helps to assess whether protein mutations a®ect the occurrence of sequence-architectural features (globular domains, targeting signals, post-translational modi¯cation sites, etc.). As input, HPMV accepts protein mutations À À À as UniProt accessions with mutations (e.g. HGVS nomenclature), genome coordinates, or FASTA sequences. As output, HPMV provides an interactive cartoon showing the mutations in relation to elements of the sequence architecture. A large variety of protein sequence architectural features were selected for their particular relevance to mutation interpretation. Clicking a sequence feature in the cartoon expands a tree view of additional This is an Open Access article published by World Scienti¯c Publishing Company. It is distributed under the terms of the Creative Commons Attribution 3.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited. Vol. 13, No. 5 (2015) 1550028 (18 pages information including multiple sequence alignments of conserved domains and a simple 3D viewer mapping the mutation to known PDB structures, if available. The cartoon is also correlated with a multiple sequence alignment of similar sequences from other organisms. In cases where a mutation is likely to have a straightforward interpretation (e.g. a point mutation disrupting a well-understood targeting signal), this interpretation is suggested. The interactive cartoon can be downloaded as standalone viewer in Java jar format to be saved and viewed later with only a standard Java runtime environment. The HPMV website is: http://hpmv.bii. a-star.edu.sg/. Journal of Bioinformatics and Computational Biology

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Mutations in the Gene for the B-Subunit of Rod Photoreceptor Cgmp-Specific Phosphodiesterase (PDEB) in Patients with Retinal Dystrophies and Dysfunctions

Cited by 8 publications

References 24 publications

Evaluation of the Rhodopsin Kinase Gene in Patients with Retinitis Pigmentosa

Evaluation of the Rhodopsin Kinase Gene in Patients with Retinitis Pigmentosa

Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia

HPMV: Human protein mutation viewer — relating sequence mutations to protein sequence architecture and function changes

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