Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein

被引:100
作者
Isosomppi, J
Vesa, J
Jalanko, A
Peltonen, L
机构
[1] Univ Helsinki, Acad Finland,Biomedicum, Natl Publ Hlth Inst, Dept Mol Med, FIN-00251 Helsinki, Finland
[2] Univ Helsinki, Acad Finland,Biomedicum, Ctr Excellence Dis Genet, Dept Med Genet, FIN-00251 Helsinki, Finland
[3] Univ Calif Los Angeles, Sch Med, Gonda Neurosci & Genet Res Ctr, Dept Human Genet, Los Angeles, CA 90095 USA
基金
芬兰科学院;
关键词
D O I
10.1093/hmg/11.8.885
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCL) belongs to the neuronal ceroid lipofuscinosis group of common recessively inherited neurodegenerative disorders. The CLN5 gene responsible for this brain disorder codes for a novel protein with no homology to previously reported proteins. In this study, we have investigated the biosynthesis and intracellular localization of this protein in transiently transfected BHK-21 cells using a CLN5-specific peptide antibody. Confocal immunofluorescence microscopy showed that wild-type CLN5 is predominantly targeted to lysosomes and immunoprecipitation analysis recognized a 60 kDa polypeptide. The molecular weight of this protein was reduced to 40 kDa by deglycosylation with Endo H and to 38 kDa with PNGase F. The same-sized glycosylated polypeptides were also observed in the media, suggesting that the 60 kDa glycosylated CLN5 polypeptide represents a soluble lysosomal glycoprotein, not an integral transmembrane protein as predicted earlier. The most common human vLINCL mutation blocked the lysosomal targeting of expressed polypeptides. This would imply that the pathogenesis of vLINCL would be associated with the defective lysosomal trafficking, preventing the normal biological function of the corresponding polypeptide.
引用
收藏
页码:885 / 891
页数:7
相关论文
共 35 条
[1]   JANSKY-BIELSCHOWSKY VARIANT DISEASE - CT, MRI, AND SPECT FINDINGS [J].
AUTTI, T ;
RAININKO, R ;
LAUNES, J ;
NUUTILA, A ;
SANTAVUORI, P .
PEDIATRIC NEUROLOGY, 1992, 8 (02) :121-126
[2]   Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse [J].
Gao, HL ;
Boustany, RMN ;
Espinola, JA ;
Cotman, SL ;
Srinidhi, L ;
Antonellis, KA ;
Gillis, T ;
Qin, XB ;
Liu, SM ;
Donahue, LR ;
Bronson, RT ;
Faust, JR ;
Stout, D ;
Haines, JL ;
Lerner, TJ ;
MacDonald, ME .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (02) :324-335
[3]  
Heinonen O, 2000, J COMP NEUROL, V426, P406, DOI 10.1002/1096-9861(20001023)426:3<406::AID-CNE5>3.0.CO
[4]  
2-5
[5]   Expression of palmitoyl protein thioesterase in neurons [J].
Heinonen, O ;
Kyttälä, A ;
Lehmus, E ;
Paunio, T ;
Peltonen, L ;
Jalanko, A .
MOLECULAR GENETICS AND METABOLISM, 2000, 69 (02) :123-129
[6]   Human palmitoyl protein thioesterase: Evidence for lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis [J].
Hellsten, E ;
Vesa, J ;
Olkkonen, VM ;
Jalanko, A ;
Peltonen, L .
EMBO JOURNAL, 1996, 15 (19) :5240-5245
[7]   SOSUI: classification and secondary structure prediction system for membrane proteins [J].
Hirokawa, T ;
Boon-Chieng, S ;
Mitaku, S .
BIOINFORMATICS, 1998, 14 (04) :378-379
[8]   Phenotype-genotype correlation in eight patients with Finnish variant late infantile NCL (CLN5) [J].
Holmberg, V ;
Lauronen, L ;
Autti, T ;
Santavuori, P ;
Savukoski, M ;
Uvebrant, F ;
Hofman, I ;
Peltonen, L ;
Järvelä, I .
NEUROLOGY, 2000, 55 (04) :579-581
[9]   Defective intracellular transport of CLN3 is the molecular basis of Batten disease (JNCL) [J].
Järvelä, I ;
Lehtovirta, M ;
Tikkanen, R ;
Kyttälä, A ;
Jalanko, A .
HUMAN MOLECULAR GENETICS, 1999, 8 (06) :1091-1098
[10]   Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease [J].
Järvelä, I ;
Sainio, M ;
Rantamäki, T ;
Olkkonen, VM ;
Carpén, O ;
Peltonen, L ;
Jalanko, A .
HUMAN MOLECULAR GENETICS, 1998, 7 (01) :85-90