Jules, Félix; Sauvageau, Etienne; Dumaresq-Doiron, Karine; Mazzaferri, Javier; Haug-Kroper, Martina; Fluhrer, Regina; Costantino, Santiago et Lefrancois, Stephane (2017). CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble protein Experimental Cell Research , vol. 357 , nº 1. pp. 40-50. DOI: 10.1016/j.yexcr.2017.04.024.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
The Neuronal ceroid lipofuscinoses (NCLs) are a group of recessive disorders of childhood with overlapping symptoms including vision loss, ataxia, cognitive regression and premature death. 14 different genes have been linked to NCLs (CLN1-CLN14), but the functions of the proteins encoded by the majority of these genes have not been fully elucidated. Mutations in the CLN5 gene are responsible for the Finnish variant late-infantile form of NCL (Finnish vLINCL). CLN5 is translated as a 407 amino acid transmembrane domain containing protein that is heavily glycosylated, and subsequently cleaved into a mature soluble protein. Functionally, CLN5 is implicated in the recruitment of the retromer complex to endosomes, which is required to sort the lysosomal sorting receptors from endosomes to the trans-Golgi network. The mechanism that processes CLN5 into a mature soluble protein is currently not known. Herein, we demonstrate that CLN5 is initially translated as a type II transmembrane protein and subsequently cleaved by SPPL3, a member of the SPP/SPPL intramembrane protease family, into a mature soluble protein consisting of residues 93-407. The remaining N-terminal fragment is then cleaved by SPPL3 and SPPL2b and degraded in the proteasome. This work further characterizes the biology of CLN5 in the hopes of identifying a novel therapeutic strategy for affected children.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Endosomes; Intracellular trafficking; Neurodegeneration; Neuronal ceroid lipofuscinosis; Signal Peptide Peptidase-like proteases |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 19 juin 2017 19:20 |
| Dernière modification: | 19 juin 2017 19:20 |
| URI: | https://espace.inrs.ca/id/eprint/5381 |
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