![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 13, Issue 9, 3355-3368, September 2002
§ and
*Centre for High Resolution Imaging and Processing, School of Life
Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK;
In LAMP-2-deficient mice autophagic vacuoles accumulate in many
tissues, including liver, pancreas, muscle, and heart. Here we extend
the phenotype analysis using cultured hepatocytes. In LAMP-2-deficient
hepatocytes the half-life of both early and late autophagic vacuoles
was prolonged as evaluated by quantitative electron microscopy.
However, an endocytic tracer reached the autophagic vacuoles,
indicating delivery of endo/lysosomal constituents to autophagic
vacuoles. Enzyme activity measurements showed that the trafficking of
some lysosomal enzymes to lysosomes was impaired. Immunoprecipitation
of metabolically labeled cathepsin D indicated reduced intracellular
retention and processing in the knockout cells. The steady-state level
of 300-kDa mannose 6-phosphate receptor was slightly lower in
LAMP-2-deficient hepatocytes, whereas that of 46-kDa mannose
6-phosphate receptor was decreased to 30% of controls due to a shorter
half-life. Less receptor was found in the Golgi region and in vesicles
and tubules surrounding multivesicular endosomes, suggesting impaired
recycling from endosomes to the Golgi. More receptor was found in
autophagic vacuoles, which may explain its shorter half-life. Our data
indicate that in hepatocytes LAMP-2 deficiency either directly or
indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate
receptors and partial mistargeting of a subset of lysosomal enzymes.
Autophagic vacuoles may accumulate due to impaired capacity for
lysosomal degradation.
Zentrum Biochemie und Molekulare Zellbiologie, Abt.
Biochemie II, Universität Göttingen, 37073 Göttingen,
Germany; §Graduate School of Pharmaceutical Sciences,
Pharmaceutical Cell Biology, Kyushu University, Fukuoka, Japan;
¶Kekule Institut für Organische Chemie und Biochemie
der Universität, D-53121 Bonn, Germany; and
#Biochemisches Institut, Universität Kiel, D-24098
Kiel, Germany
Corresponding author. E-mail address:
psaftig{at}biochem.uni-kiel.de.
Both authors contributed equally to this work.
This article has been cited by other articles:
|
|
 |
|
  F. Okamoto, H. Kajiya, K. Toh, S. Uchida, M. Yoshikawa, S. Sasaki, M. A. Kido, T. Tanaka, and K. Okabe Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclasts Am J Physiol Cell Physiol, March 1, 2008; 294(3): C693 - C701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Beertsen, M. Willenborg, V. Everts, A. Zirogianni, R. Podschun, B. Schroder, E.-L. Eskelinen, and P. Saftig Impaired Phagosomal Maturation in Neutrophils Leads to Periodontitis in Lysosomal-Associated Membrane Protein-2 Knockout Mice J. Immunol., January 1, 2008; 180(1): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. David, M.-C. Tiveron, A. Defays, C. Beclin, V. Camosseto, E. Gatti, H. Cremer, and P. Pierre BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons J. Cell Sci., January 15, 2007; 120(2): 353 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Demarchi, C. Bertoli, T. Copetti, I. Tanida, C. Brancolini, E.-L. Eskelinen, and C. Schneider Calpain is required for macroautophagy in mammalian cells J. Cell Biol., November 20, 2006; 175(4): 595 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Corcelle, M. Nebout, S. Bekri, N. Gauthier, P. Hofman, P. Poujeol, P. Fenichel, and B. Mograbi Disruption of Autophagy at the Maturation Step by the Carcinogen Lindane Is Associated with the Sustained Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Activity. Cancer Res., July 1, 2006; 66(13): 6861 - 6870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Massey, S. Kaushik, G. Sovak, R. Kiffin, and A. M. Cuervo Consequences of the selective blockage of chaperone-mediated autophagy PNAS, April 11, 2006; 103(15): 5805 - 5810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Malorni and C. Fiorentini Is the Rac GTPase-activating toxin CNF1 a smart hijacker of host cell fate? FASEB J, April 1, 2006; 20(6): 606 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fanin, A. C. Nascimbeni, L. Fulizio, M. Spinazzi, P. Melacini, and C. Angelini Generalized Lysosome-Associated Membrane Protein-2 Defect Explains Multisystem Clinical Involvement and Allows Leukocyte Diagnostic Screening in Danon Disease Am. J. Pathol., April 1, 2006; 168(4): 1309 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-A. Gonzalez-Polo, P. Boya, A.-L. Pauleau, A. Jalil, N. Larochette, S. Souquere, E.-L. Eskelinen, G. Pierron, P. Saftig, and G. Kroemer The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death J. Cell Sci., July 15, 2005; 118(14): 3091 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lajoie, G. Guay, J. W. Dennis, and I. R. Nabi The lipid composition of autophagic vacuoles regulates expression of multilamellar bodies J. Cell Sci., May 1, 2005; 118(9): 1991 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Styers, G. Salazar, R. Love, A. A. Peden, A. P. Kowalczyk, and V. Faundez The Endo-Lysosomal Sorting Machinery Interacts with the Intermediate Filament Cytoskeleton Mol. Biol. Cell, December 1, 2004; 15(12): 5369 - 5382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Esselens, V. Oorschot, V. Baert, T. Raemaekers, K. Spittaels, L. Serneels, H. Zheng, P. Saftig, B. De Strooper, J. Klumperman, et al. Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway J. Cell Biol., September 27, 2004; 166(7): 1041 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kokkonen, A. Rivinoja, A. Kauppila, M. Suokas, I. Kellokumpu, and S. Kellokumpu Defective Acidification of Intracellular Organelles Results in Aberrant Secretion of Cathepsin D in Cancer Cells J. Biol. Chem., September 17, 2004; 279(38): 39982 - 39988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jager, C. Bucci, I. Tanida, T. Ueno, E. Kominami, P. Saftig, and E.-L. Eskelinen Role for Rab7 in maturation of late autophagic vacuoles J. Cell Sci., September 15, 2004; 117(20): 4837 - 4848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Atlashkin, V. Kreykenbohm, E.-L. Eskelinen, D. Wenzel, A. Fayyazi, and G. Fischer von Mollard Deletion of the SNARE vti1b in Mice Results in the Loss of a Single SNARE Partner, Syntaxin 8 Mol. Cell. Biol., August 1, 2003; 23(15): 5198 - 5207. [Abstract] [Full Text] [PDF]
|
|
