Journal article
Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia
Molecular and cellular neurosciences, Vol.64, pp.1-8
01/2015
DOI: 10.1016/j.mcn.2014.10.007
PMCID: PMC4323879
PMID: 25461672
Abstract
Phosphodiesterase-6 (PDE6) is an essential effector enzyme 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 Xenopus 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.
•Achromatopsia-linked mutants of cone PDE6 were expressed in rods of transgenic frogs.•PDE6 mutants were examined for their stability and compartmentalization.•A spectrum of mechanisms of missense PDE6C mutations in achromatopsia is proposed.
Details
- Title: Subtitle
- Distinct patterns of compartmentalization and proteolytic stability of PDE6C mutants linked to achromatopsia
- Creators
- Pallavi Cheguru - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United StatesAnurima Majumder - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United StatesNikolai O Artemyev - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular neurosciences, Vol.64, pp.1-8
- DOI
- 10.1016/j.mcn.2014.10.007
- PMID
- 25461672
- PMCID
- PMC4323879
- NLM abbreviation
- Mol Cell Neurosci
- ISSN
- 1044-7431
- eISSN
- 1095-9327
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000009, name: National Institutes of Health, award: EY-10843
- Language
- English
- Date published
- 01/2015
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025368402771
Metrics
29 Record Views