HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		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 Citation Map Services Email this article to a friend 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 Pshezhetsky, AlexeyV. Articles by Potier, M. Search for Related Content PubMed PubMed Citation Articles by Pshezhetsky, AlexeyV. Articles by Potier, M. Social Bookmarking                      What's this?

Volume 271, Number 45, Issue of November 8, 1996 pp. 28359-28365
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of -Galactosidase, Cathepsin A, and Neuraminidase
POSSIBLE IMPLICATION FOR INTRALYSOSOMAL CATABOLISM OF KERATAN SULFATE

(Received for publication, November 6, 1995, and in revised form, May 15, 1996)

From the Service de Génétique Médicale, Hôpital Sainte-Justine, and Département de Pédiatrie, Faculté de Médicine, Université de Montréal, Montréal, Québec, Canada H3T 1C5

N-Acetylgalactosamine-6-sulfate sulfatase (GALNS) catalyzes the first step of intralysosomal keratan sulfate (KS) catabolism. In Morquio type A syndrome GALNS deficiency causes the accumulation of KS in tissues and results in generalized skeletal dysplasia in affected patients. We show that in normal cells GALNS is in a 1.27-MDa complex with three other lysosomal hydrolases: -galactosidase, -neuraminidase, and cathepsin A (protective protein). GALNS copurifies with the complex by different chromatography techniques: affinity chromatography on both cathepsin A-binding and -galactosidase-binding columns, gel filtration, and chromatofocusing. Anti-human cathepsin A rabbit antiserum coprecipitates GALNS together with cathepsin A, -galactosidase, and -neuraminidase in both a purified preparation of the 1.27-MDa complex and crude glycoprotein fraction from human placenta extract. Gel filtration analysis of fibroblast extracts of patients deficient in either -galactosidase (-galactosidosis) or cathepsin A (galactosialidosis), which accumulate KS, demonstrates that the 1.27-MDa complex is disrupted and that GALNS is present only in free homodimeric form. The GALNS activity and cross-reacting material are reduced in the fibroblasts of patients affected with galactosialidosis, indicating that the complex with cathepsin A may protect GALNS in the lysosome. We suggest that the 1.27-MDa complex of lysosomal hydrolases is essential for KS catabolism and that the disruption of this complex may be responsible for the KS accumulation in -galactosidosis and galactosialidosis patients.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Seyrantepe, A. Hinek, J. Peng, M. Fedjaev, S. Ernest, Y. Kadota, M. Canuel, K. Itoh, C. R. Morales, J. Lavoie, et al. Enzymatic Activity of Lysosomal Carboxypeptidase (Cathepsin) A Is Required for Proper Elastic Fiber Formation and Inactivation of Endothelin-1 Circulation, April 15, 2008; 117(15): 1973 - 1981. [Abstract] [Full Text] [PDF]

				B. Winchester Lysosomal metabolism of glycoproteins Glycobiology, June 1, 2005; 15(6): 1R - 15R. [Abstract] [Full Text] [PDF]

				Y. Sun, X. Qi, and G. A. Grabowski Saposin C Is Required for Normal Resistance of Acid {beta}-Glucosidase to Proteolytic Degradation J. Biol. Chem., August 22, 2003; 278(34): 31918 - 31923. [Abstract] [Full Text] [PDF]

				K. E. Lukong, V. Seyrantepe, K. Landry, S. Trudel, A. Ahmad, W. A. Gahl, S. Lefrancois, C. R. Morales, and A. V. Pshezhetsky Intracellular Distribution of Lysosomal Sialidase Is Controlled by the Internalization Signal in Its Cytoplasmic Tail J. Biol. Chem., November 30, 2001; 276(49): 46172 - 46181. [Abstract] [Full Text] [PDF]

				Erik. J. Bonten, W. F. Arts, M. Beck, A. Covanis, M. A. Donati, R. Parini, E. Zammarchi, and A. d'Azzo Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis Hum. Mol. Genet., November 1, 2000; 9(18): 2715 - 2725. [Abstract] [Full Text] [PDF]

				K. E. Lukong, M.-A. Elsliger, Y. Chang, C. Richard, G. Thomas, W. Carey, A. Tylki-Szymanska, B. Czartoryska, T. Buchholz, G. R. Criado, et al. Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex Hum. Mol. Genet., April 12, 2000; 9(7): 1075 - 1085. [Abstract] [Full Text] [PDF]

				A. van der Spoel, E. Bonten, and A. d'Azzo Processing of Lysosomal beta -Galactosidase. THE C-TERMINAL PRECURSOR FRAGMENT IS AN ESSENTIAL DOMAIN OF THE MATURE ENZYME J. Biol. Chem., March 31, 2000; 275(14): 10035 - 10040. [Abstract] [Full Text] [PDF]

				R. Gingras, C. Richard, M. El-Alfy, C. R. Morales, M. Potier, and A. V. Pshezhetsky Purification, cDNA Cloning, and Expression of a New Human Blood Plasma Glutamate Carboxypeptidase Homologous to N-Acetyl-aspartyl-{alpha}-glutamate Carboxypeptidase/Prostate-specific Membrane Antigen J. Biol. Chem., April 23, 1999; 274(17): 11742 - 11750. [Abstract] [Full Text] [PDF]

				E. J. Bonten and A. d'Azzo Lysosomal Neuraminidase. CATALYTIC ACTIVATION IN INSECT CELLS IS CONTROLLED BY THE PROTECTIVE PROTEIN/CATHEPSIN A J. Biol. Chem., November 22, 2000; 275(48): 37657 - 37663. [Abstract] [Full Text] [PDF]

				K. E. Lukong, K. Landry, M.-A. Elsliger, Y. Chang, S. Lefrancois, C. R. Morales, and A. V. Pshezhetsky Mutations in Sialidosis Impair Sialidase Binding to the Lysosomal Multienzyme Complex J. Biol. Chem., May 11, 2001; 276(20): 17286 - 17290. [Abstract] [Full Text] [PDF]