The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5

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Show simple item record Moharir, Akshay Peck, Sun H. Budden, Theodore Lee, Stella Y. 2013-10-11T18:37:11Z 2013-10-11T18:37:11Z 2013-10-11
dc.description.abstract CLN5 is a soluble lysosomal protein with unknown function. Mutations in CLN5 lead to neuronal ceroid lipofuscinosis, a group of inherited neurodegenerative disorders that mainly affect children. CLN5 has eight potential N-glycosylation sites based on the Asn-X-Thr/Ser consensus sequence. Through site-directed mutagenesis of individual asparagine residues to glutamine on each of the N-glycosylation consensus sites, we showed that all eight putative N-glycosylation sites are utilized in vivo. Additionally, localization studies showed that the lack of N-glycosylation on certain sites (N179, N252, N304, or N320) caused CLN5 retention in the endoplasmic reticulum, indicating that glycosylation is important for protein folding. Interestingly, one particular mutant, N401Q, is mislocalized to the Golgi, suggesting that N401 is not important for protein folding but essential for CLN5 trafficking to the lysosome. Finally, we analyzed several patient mutations in which N-glycosylation is affected. The N192S patient mutant is localized to the lysosome, indicating that this mutant has a functional defect in the lysosome. Our results suggest that there are functional differences in various N-glycosylation sites of CLN5 which affect folding, trafficking, and lysosomal function of CLN5. en_US
dc.language.iso en_US en_US
dc.relation.uri en_US
dc.subject N-glycosylation en_US
dc.subject Lysosomal protein en_US
dc.subject CLN5 en_US
dc.subject Protein folding en_US
dc.title The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5 en_US
dc.type Article (publisher version) en_US 2013 en_US
dc.citation.doi doi:10.1371/journal.pone.0074299 en_US
dc.citation.issue 9 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.spage e74299 en_US
dc.citation.volume 8 en_US
dc.contributor.authoreid sunpeck en_US
dc.contributor.authoreid sylee en_US

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