QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vesa, J. Articles by Peltonen, L. Search for Related Content PubMed PubMed Citation Articles by Vesa, J. Articles by Peltonen, L.

Vol. 13, Issue 7, 2410-2420, July 2002

Neuronal Ceroid Lipofuscinoses Are Connected at Molecular Level: Interaction of CLN5 Protein with CLN2 and CLN3

Jouni Vesa,^* Mark H. Chin,^* Kathrin Oelgeschläger,^* Juha Isosomppi, Esteban C. DellAngelica,^* Anu Jalanko, and Leena Peltonen^*

 ^*Department of Human Genetics, University of California at Los Angeles School of Medicine, Gonda Neuroscience and Genetics Research Center, Los Angeles, California 90095-7088; and  Department of Molecular Medicine and Center of Excellence in Disease Genetics, The Academy of Finland, Biomedicum, National Public Health Institute, FIN-00300 Helsinki, Finland

Neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative storage diseases characterized by mental retardation, visual failure, and brain atrophy as well as accumulation of storage material in multiple cell types. The diseases are caused by mutations in the ubiquitously expressed genes, of which six are known. Herein, we report that three NCL disease forms with similar tissue pathology are connected at the molecular level: CLN5 polypeptides directly interact with the CLN2 and CLN3 proteins based on coimmunoprecipitation and in vitro binding assays. Furthermore, disease mutations in CLN5 abolished interaction with CLN2, while not affecting association with CLN3. The molecular characterization of CLN5 revealed that it was synthesized as four precursor forms, due to usage of alternative initiator methionines in translation. All forms were targeted to lysosomes and the longest form, translated from the first potential methionine, was associated with membranes. Interactions between CLN polypeptides were shown to occur with this longest, membrane-bound form of CLN5. Both intracellular targeting and posttranslational glycosylation of the polypeptides carrying human disease mutations were similar to wild-type CLN5.

---

Corresponding author. E-mail address: lpeltonen{at}mednet.ucla.edu.

---

Molecular Biology of the Cell
Vol. 13, 2410-2420, July 2002
Copyright © 2002 by The American Society for Cell Biology

This article has been cited by other articles:

				J.-W. Chang, H. Choi, H.-J. Kim, D.-G. Jo, Y.-J. Jeon, J.-Y. Noh, W. J. Park, and Y.-K. Jung Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin Hum. Mol. Genet., February 1, 2007; 16(3): 317 - 326. [Abstract] [Full Text] [PDF]

				C. Drogemuller, A. Wohlke, and O. Distl Characterization of Candidate Genes for Neuronal Ceroid Lipofuscinosis in Dog J. Hered., November 1, 2005; 96(7): 735 - 738. [Abstract] [Full Text] [PDF]

				N. Pineda-Trujillo, W. Cornejo, J. Carrizosa, R. B. Wheeler, S. Munera, A. Valencia, J. Agudelo-Arango, A. Cogollo, G. Anderson, G. Bedoya, et al. A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset Neurology, February 22, 2005; 64(4): 740 - 742. [Abstract] [Full Text] [PDF]

				O. Kopra, J. Vesa, C. von Schantz, T. Manninen, H. Minye, A.-L. Fabritius, J. Rapola, O. P. v. Diggelen, J. Saarela, A. Jalanko, et al. A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging Hum. Mol. Genet., December 1, 2004; 13(23): 2893 - 2906. [Abstract] [Full Text] [PDF]

				J. L. Griffin, D. Muller, R. Woograsingh, V. Jowatt, A. Hindmarsh, J. K. Nicholson, and J. E. Martin Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics Physiol Genomics, December 3, 2002; 11(3): 195 - 203. [Abstract] [Full Text] [PDF]

				S. L. Cotman, V. Vrbanac, L.-A. Lebel, R. L. Lee, K. A. Johnson, L.-R. Donahue, A. M. Teed, K. Antonellis, R. T. Bronson, T. J. Lerner, et al. Cln3 {Delta}ex7/8 knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth Hum. Mol. Genet., October 15, 2002; 11(22): 2709 - 2721. [Abstract] [Full Text] [PDF]