The PDE6 mutation in the rd10 retinal degeneration mouse model causes protein mislocalization and instability and promotes cell death through increased ion influx

• Published in: The Journal of biological chemistry Vol. 293; no. 40; pp. 15332 - 15346
• Main Authors: Wang, Tian, Reingruber, Jürgen, Woodruff, Michael L., Majumder, Anurima, Camarena, Andres, Artemyev, Nikolai O., Fain, Gordon L., Chen, Jeannie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.10.2018; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Calcium - metabolism; Cell Death; cGMP-gated channels; cyclic GMP (cGMP); Cyclic GMP - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 6 - deficiency; Cyclic Nucleotide Phosphodiesterases, Type 6 - genetics; Cyclic Nucleotide-Gated Cation Channels - deficiency; Cyclic Nucleotide-Gated Cation Channels - genetics; Disease Models, Animal; Gene Expression Regulation; Ion Transport; Membrane Potentials - physiology; Mice; Mice, Knockout; missense mutation; Molecular Bases of Disease; Mutation, Missense; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; PDE6; phosphodiesterases; photoreceptor; phototransduction; protein mislocalization; Protein Stability; protein translocation; Protein Transport; retinal degeneration; Retinal Degeneration - genetics; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Rod Photoreceptor Cells - metabolism; Retinal Rod Photoreceptor Cells - pathology; Signal Transduction; Single-Cell Analysis; Time Factors; PDE6; protein transport; retinal degeneration; cell death; photoreceptor; cGMP-gated channels; protein stability; phototransduction; missense mutation; protein translocation; cyclic GMP (cGMP); phosphodiesterases; protein mislocalization

The retinal degeneration model rd10 contains a missense mutation of the catalytic PDE6 β subunit, which hydrolyzes cGMP in response to light. This model produces cell death more slowly than others caused by PDE6 loss of function, making it of particular interest for studying potential therapeutics....