%0 Journal Article
%A Jules, Felix
%A Sauvageau, Etienne
%A Dumaresq-Doiron, Karine
%A Mazzaferri, Javier
%A Haug-Kröper, Martina
%A Fluhrer, Regina
%A Costantino, Santiago
%A Lefrancois, Stephane
%T CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble protein.
%J Experimental cell research
%V 357
%N 1
%@ 0014-4827
%C Orlando, Fla.
%I Academic Press
%M DZNE-2020-05660
%P 40-50
%D 2017
%X 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.
%K Lysosome-Associated Membrane Glycoproteins
%K Aspartic Acid Endopeptidases: metabolism
%K Cell Line
%K Endosomes: metabolism
%K Humans
%K Lysosomes: metabolism
%K Membrane Proteins: metabolism
%K Neuronal Ceroid-Lipofuscinoses: metabolism
%K Protein Transport
%K Solubility
%K trans-Golgi Network: metabolism
%K CLN5 protein, human (NLM Chemicals)
%K Membrane Proteins (NLM Chemicals)
%K Aspartic Acid Endopeptidases (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28442266
%R 10.1016/j.yexcr.2017.04.024
%U https://pub.dzne.de/record/139338