Publication date: Available online 22 April 2017
Source:Experimental Cell Research
Author(s): Felix Jules, Etienne Sauvageau, Karine Dumaresq-Doiron, Javier Mazzaferri, Martina Haug-Kröper, Regina Fluhrer, Santiago Costantino, Stephane Lefrancois
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.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2p2SPcF
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Objective Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation...
-
Abstract Purpose Overcoming the flaws of current data management conditions in head and neck oncology could enable integrated informatio...
-
Vol.31 No.5 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1k8FKtW via IFTTT
-
Universal newborn hearing screening (UNHS) has become the standard of care in many countries. The aim of this study was to evaluate the resu...
-
Geographic region: Does it matter in cutaneous melanoma of the head and neck? Laryngoscope. 2017 Jun 05;: Authors: Kılıç S, Unsal AA,...
-
The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of lichen sclerosus (LS)...
-
Abstract The head-mounted display (HMD) has the potential to improve the quality of ultrasound-guided procedures. The aim of this non-clin...
-
http://ift.tt/2pnwWaQ
-
Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου