|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 32, 24829-24839, August 11, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Anatomy and Cell Biology, McGill University,
Montreal, Quebec H3A 2B2, Canada
Prosaposin is synthesized as a 53-kDa protein,
post-translationally modified to a 65-kDa form and further glycosylated
to a 70-kDa secretory product. The 65-kDa protein is associated to Golgi membranes and is targeted to lysosomes, where four smaller nonenzymatic saposins implicated in the hydrolysis of sphingolipids are
generated by its partial proteolysis. The targeting of the 65-kDa
protein to lysosomes is not mediated by the mannose 6-phosphate receptor. The Golgi apparatus appears to accomplish the molecular sorting of the 65-kDa prosaposin by decoding a signal from its amino
acid backbone. This investigation deals with the characterization of
the sequence involved in this process by deleting the saposin functional domains A, B, C, and D and the highly conserved N and C
termini of prosaposin. The truncated cDNAs were subcloned into expression vectors and transfected to COS-7 cells. The destination of
the mutated proteins was assessed by immunocytochemistry. Deletion of
the C terminus did not interfere with the secretion of prosaposin but
abolished its transport to lysosomes. Deletion of saposins and the
N-terminal domain did not affect the lysosomal or secretory routing of
prosaposin. A chimeric construct of albumin and the C terminus of
prosaposin was not directed to lysosomes. However, albumin connected to
the C terminus and one or more functional domains of prosaposin reached
lysosomes, indicating that the C terminus and at least one saposin
domain are required for this process. In summary, we are reporting a
novel sequence involved in the targeting of prosaposin to lysosomes.
Identification of a Novel Sequence Involved in Lysosomal Sorting
of the Sphingolipid Activator Protein Prosaposin*
*
This work was supported by the Medical Research Council,
Canada.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Fellow of Fonds de la Recherche en Santé du
Québec. To whom correspondence should be addressed: Dept. of
Anatomy and Cell Biology, McGill University, 3640 University St.,
Montreal, Quebec H3A 2B2, Canada. Tel.: 514-398-6398; Fax:
514-398-5047; E-mail: cxco@musica.mcgill.ca.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Seyrantepe, M. Canuel, S. Carpentier, K. Landry, S. Durand, F. Liang, J. Zeng, A. Caqueret, R. A. Gravel, S. Marchesini, et al. Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage Hum. Mol. Genet., June 1, 2008; 17(11): 1556 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, D. P. Witte, M. Zamzow, H. Ran, B. Quinn, J. Matsuda, and G. A. Grabowski Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and {alpha}-hydroxy ceramide accumulation, and altered prosaposin trafficking Hum. Mol. Genet., April 15, 2007; 16(8): 957 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Madriz, M. B. Martinez, M. A. Rodriguez, G. Sierra, C. Martinez-Lopez, A. M. Riveron, L. Flores, and E. Orozco Expression in fibroblasts and in live animals of Entamoeba histolytica polypeptides EhCP112 and EhADH112 Microbiology, May 1, 2004; 150(5): 1251 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhou, C. Cantu III, Y. Sagiv, N. Schrantz, A. B. Kulkarni, X. Qi, D. J. Mahuran, C. R. Morales, G. A. Grabowski, K. Benlagha, et al. Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins Science, January 23, 2004; 303(5657): 523 - 527. [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]
|
|
|
|
 |
|
 J. Piatigorsky, B. Norman, L. J. Dishaw, L. Kos, J. Horwitz, P. J. Steinbach, and Z. Kozmik J3-crystallin of the jellyfish lens: Similarity to saposins PNAS, October 23, 2001; 98(22): 12362 - 12367. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |