Cell biology and function of neuronal ceroid lipofuscinosis-related proteins

TY - JOUR

T1 - Cell biology and function of neuronal ceroid lipofuscinosis-related proteins

AU - Kollmann, Katrin

AU - Uusi-Rauva, Kristiina

AU - Scifo, Enzo

AU - Tyynelä, Jaana

AU - Jalanko, Anu

AU - Braulke, Thomas

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Neuronal ceroid lipofuscinoses (NCL) comprise a group of inherited lysosomal disorders with variable age of onset, characterized by lysosomal accumulation of autofluorescent ceroid lipopigments, neuroinflammation, photoreceptor- and neurodegeneration. Most of the NCL-related genes encode soluble and transmembrane proteins which localize to the endoplasmic reticulum or to the endosomal/lysosomal compartment and directly or indirectly regulate lysosomal function. Recently, exome sequencing led to the identification of four novel gene defects in NCL patients and a new NCL nomenclature currently comprising CLN1 through CLN14. Although the precise function of most of the NCL proteins remains elusive, comprehensive analyses of model organisms, particularly mouse models, provided new insight into pathogenic mechanisms of NCL diseases and roles of mutant NCL proteins in cellular/subcellular protein and lipid homeostasis, as well as their adaptive/compensatorial regulation at the transcriptional level. This review summarizes the current knowledge on the expression, function and regulation of NCL proteins and their impact on lysosomal integrity. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

AB - Neuronal ceroid lipofuscinoses (NCL) comprise a group of inherited lysosomal disorders with variable age of onset, characterized by lysosomal accumulation of autofluorescent ceroid lipopigments, neuroinflammation, photoreceptor- and neurodegeneration. Most of the NCL-related genes encode soluble and transmembrane proteins which localize to the endoplasmic reticulum or to the endosomal/lysosomal compartment and directly or indirectly regulate lysosomal function. Recently, exome sequencing led to the identification of four novel gene defects in NCL patients and a new NCL nomenclature currently comprising CLN1 through CLN14. Although the precise function of most of the NCL proteins remains elusive, comprehensive analyses of model organisms, particularly mouse models, provided new insight into pathogenic mechanisms of NCL diseases and roles of mutant NCL proteins in cellular/subcellular protein and lipid homeostasis, as well as their adaptive/compensatorial regulation at the transcriptional level. This review summarizes the current knowledge on the expression, function and regulation of NCL proteins and their impact on lysosomal integrity. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

KW - Animals

KW - Humans

KW - Membrane Proteins

KW - Mice

KW - Neuronal Ceroid-Lipofuscinoses

KW - Thiolester Hydrolases

U2 - 10.1016/j.bbadis.2013.01.019

DO - 10.1016/j.bbadis.2013.01.019

M3 - SCORING: Journal article

C2 - 23402926

VL - 1832

SP - 1866

EP - 1881

JO - BBA-MOL BASIS DIS

JF - BBA-MOL BASIS DIS

SN - 0925-4439

IS - 11

ER -