Journal Article

DZNE-2020-05660

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble protein.

Jules, F. ; Sauvageau, E. ; Dumaresq-Doiron, K. ; Mazzaferri, J. ; Haug-Kröper, M. ; Fluhrer, R.DZNE* ; Costantino, S. ; Lefrancois, S. (Corresponding author)

2017
Academic Press Orlando, Fla.

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.yexcr.2017.04.024

Abstract: 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.

Keyword(s): Lysosome-Associated Membrane Glycoproteins (MeSH) ; Aspartic Acid Endopeptidases: metabolism (MeSH) ; Cell Line (MeSH) ; Endosomes: metabolism (MeSH) ; Humans (MeSH) ; Lysosomes: metabolism (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Neuronal Ceroid-Lipofuscinoses: metabolism (MeSH) ; Protein Transport (MeSH) ; Solubility (MeSH) ; trans-Golgi Network: metabolism (MeSH) ; CLN5 protein, human ; Membrane Proteins ; Aspartic Acid Endopeptidases

---

Contributing Institute(s):

1. Signal Peptide Peptidases as Models for γ-Secretase (AG Fluhrer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

---