Palmitoylation of Progressive Rod-Cone Degeneration (PRCD) Regulates Protein Stability and Localization.
Progressive rod-cone degeneration (PRCD) is a photoreceptor outer segment (OS) disc-specific protein with unknown function that is associated with retinitis pigmentosa (RP). The most common mutation in PRCD linked with severe RP phenotype is substitution of the only cysteine to tyrosine (C2Y). In this study, we find that PRCD is post-translationally modified by a palmitoyl lipid group at the cysteine residue linked with RP. Disrupting PRCD palmitoylation either chemically or by genetically eliminating the modified cysteine dramatically affects the stability of PRCD. Furthermore, in vivo electroporation of PRCD C2Y mutant in the mouse retina demonstrates that the palmitoylation of PRCD is important for its proper localization in the photoreceptor OS. Mutant PRCD C2Y was found in the inner segment in contrast to normal localization of WT PRCD in the OS. Our results also suggest that zDHHC3, a palmitoyl acyltransferase (PAT), catalyzes the palmitoylation of PRCD in the Golgi compartment. In conclusion, we find that the palmitoylation of PRCD is crucial for its trafficking to the photoreceptor OS and mislocalization of this protein likely leads to RP-related phenotypes.
From the Department of Ophthalmology, West Virginia University Eye institute, Morgantown, West Virginia 26506.
Joseph
J
Murphy
From the Department of Ophthalmology, West Virginia University Eye institute, Morgantown, West Virginia 26506 kolandaivelus@wvuhealthcare.com.
Saravanan
S
Kolandaivelu
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D055550:Protein Stability; D021381:Protein Transport; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D005136:Eye Proteins; D008565:Membrane Proteins; C583558:PRCD protein, human; C000619075:PRCD protein, mouse; D000217:Acyltransferases; C574550:ZDHHC3 protein, human
PRCD; outer segment; photoreceptor; protein palmitoylation; protein trafficking (Golgi); retina; retinal degeneration; retinitis pigmentosa