Human Molecular Genetics, 2000, Vol. 9, No. 11 1691-1697
© 2000 Oxford University Press
The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum
1Department of Molecular Genetics, Folkhälsan Institute of Genetics, 00280 Helsinki, Finland, 2Department of Medical Genetics, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland and 3National Public Health Institute, Department of Human Molecular Genetics, Mannerheimintie 166, 00300 Helsinki, Finland
Progressive epilepsy with mental retardation (EPMR) is a new member of the neuronal ceroid lipofuscinoses (NCLs). The CLN8 gene underlying EPMR was recently identified. It encodes a novel 286 amino acid transmembrane protein that contains an endoplasmic reticulum (ER)-retrieval signal (KKRP) in its C-terminus. A homozygous mutation in the orthologous mouse gene (Cln8) underlies the phenotype of a naturally occurring NCL model, the motor neuron degeneration mouse (mnd). To characterize the product of the CLN8 gene and to determine its intracellular localization, we expressed CLN8 cDNA in BHK, HeLa and CHO cell lines. In western blotting and pulse–chase analyses an ~33 kDa protein that does not undergo proteolytic processing steps was detected. Using CLN8 and cell organelle specific antibodies with confocal immunofluorescence microscopy the CLN8 protein was shown to localize in the ER. Partial localization to the ER–Golgi intermediate compartment (ERGIC) was also observed. The ER–ERGIC localization was not altered in the CLN8 protein representing the EPMR mutation. However, mnd mutant protein was only found in the ER. Mutations in the ER retrieval signal KKRP resulted in localization of CLN8 to the Golgi apparatus. Taken together, these data strongly suggest that CLN8 is an ER resident protein that recycles between ER and ERGIC.
+ To whom correspondence should be addressed. Tel: +358 9 47448392; Fax: +358 9 47448480; Email: anu.jalanko@ktl.fi
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Kousi, E. Siintola, L. Dvorakova, H. Vlaskova, J. Turnbull, M. Topcu, D. Yuksel, S. Gokben, B. A. Minassian, M. Elleder, et al. Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis Brain, March 1, 2009; 132(3): 810 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ramirez-Montealegre, P. G Rothberg, and D. A Pearce Another disorder finds its gene Brain, June 1, 2006; 129(6): 1353 - 1356. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gachet, S. Codlin, J. S. Hyams, and S. E. Mole btn1, the Schizosaccharomyces pombe homologue of the human Batten disease gene CLN3, regulates vacuole homeostasis J. Cell Sci., December 1, 2005; 118(23): 5525 - 5536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Heine, B. Koch, S. Storch, A. Kohlschutter, D. N. Palmer, and T. Braulke Defective Endoplasmic Reticulum-resident Membrane Protein CLN6 Affects Lysosomal Degradation of Endocytosed Arylsulfatase A J. Biol. Chem., May 21, 2004; 279(21): 22347 - 22352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Guillas, J. C. Jiang, C. Vionnet, C. Roubaty, D. Uldry, R. Chuard, J. Wang, S. M. Jazwinski, and A. Conzelmann Human Homologues of LAG1 Reconstitute Acyl-CoA-dependent Ceramide Synthesis in Yeast J. Biol. Chem., September 26, 2003; 278(39): 37083 - 37091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vesa, M. H. Chin, K. Oelgeschlager, J. Isosomppi, E. C. DellAngelica, A. Jalanko, and L. Peltonen Neuronal Ceroid Lipofuscinoses Are Connected at Molecular Level: Interaction of CLN5 Protein with CLN2 and CLN3 Mol. Biol. Cell, July 1, 2002; 13(7): 2410 - 2420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Isosomppi, J. Vesa, A. Jalanko, and L. Peltonen Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein Hum. Mol. Genet., April 15, 2002; 11(8): 885 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Luiro, O. Kopra, M. Lehtovirta, and A. Jalanko CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease Hum. Mol. Genet., September 1, 2001; 10(19): 2123 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lehtovirta, A. Kyttala, E.-L. Eskelinen, M. Hess, O. Heinonen, and A. Jalanko Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL) Hum. Mol. Genet., January 1, 2001; 10(1): 69 - 75. [Abstract] [Full Text] [PDF]
|
|