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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lefrancois, S. Articles by Morales, C. R. Search for Related Content PubMed PubMed Citation Articles by Lefrancois, S. Articles by Morales, C. R. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 40, 1593-1603, September 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Role of sphingolipids in the transport of prosaposin to the lysosomes

Correspondence to: Carlos R. Morales

Prosaposin is the precursor of four lysosomal saposins that promote the degradation of glycosphingolipids (GSLs) by acidic hydrolases. GSLs contain a hydrophobic ceramide moiety, which acts as a membrane anchor, and a hydrophilic oligosaccharide chain that faces the lumen of the Golgi apparatus and extracellular spaces. By using fumonisin B1, PDMP and D609, we tested the hypothesis that sphingolipids mediate the transport of prosaposin to the lysosomes. Fumonisin B1 interferes with the synthesis of ceramide, PDMP blocks the formation of glucosylceramide and D609 blocks the formation of sphingomyelin. Fumonisin B1 produced a 59;–85% decrease in the density of gold particles in the lysosomes of CHO and NRK cells immunolabeled with anti-prosaposin antibody, and a 55% reduction in the lysosomes of CHO cells stably transfected with an expression vector containing a human prosaposin cDNA. To examine whether the mannose 6-phosphate receptor pathway was affected by this treatment, NRK and CHO cells treated or not with fumonisin B1 were labeled with anti-cathepsin A antibody. The results showed no significant differences in labeling of the lysosomes, suggesting that the effect of fumonisin B1 was specific. When fumonisin B1 and D609 were added to the media of transfected CHO cells, a decrease in immunofluorescence with anti-prosaposin antibody was observed by confocal microscopy. PDMP did not cause any reduction in immunoreactivity, indicating that sphingolmyelin appears to be involved in this process.

In conclusion, our data support the hypothesis that sphingolipids, possibly sphingomyelin, are involved in the transport of prosaposin to the lysosomes.—Lefrancois, S., L. Michaud, M. Potier, S. Igdoura, and C. R. Morales. Role of sphingolipids in the transport of prosaposin to the lysosomes. J. Lipid Res. 1999. 40: 1593;–1603.

Supplementary key words: prosaposin, saposins, sphingolipids, lysosomal transport, fumonisin B1, PDMP, D609

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

This article has been cited by other articles:

				V. Seyrantepe, K. Landry, S. Trudel, J. A. Hassan, C. R. Morales, and A. V. Pshezhetsky Neu4, a Novel Human Lysosomal Lumen Sialidase, Confers Normal Phenotype to Sialidosis and Galactosialidosis Cells J. Biol. Chem., August 27, 2004; 279(35): 37021 - 37029. [Abstract] [Full Text] [PDF]

				S. Lefrancois, T. May, C. Knight, D. Bourbeau, and C. R. Morales The Lysosomal Transport of Prosaposin Requires the Conditional Interaction of Its Highly Conserved D Domain with Sphingomyelin J. Biol. Chem., May 3, 2002; 277(19): 17188 - 17199. [Abstract] [Full Text] [PDF]

				H. Hulkova, M. Cervenkova, J. Ledvinova, M. Tochackova, M. Hrebicek, H. Poupetova, A. Befekadu, L. Berna, B.C. Paton, K. Harzer, et al. A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation Hum. Mol. Genet., April 1, 2001; 10(9): 927 - 940. [Abstract] [Full Text] [PDF]

				Q. Zhao and C. R. Morales Identification of a Novel Sequence Involved in Lysosomal Sorting of the Sphingolipid Activator Protein Prosaposin J. Biol. Chem., August 4, 2000; 275(32): 24829 - 24839. [Abstract] [Full Text] [PDF]