Role of LAMP-2 in lysosome biogenesis and autophagy

Eeva Liisa Eskelinen, Anna Lena Illert, Yoshitaka Tanaka, Günter Schwarzmann, Judith Blanz, Kurt Von Figura, Paul Saftig

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3355-3368
Number of pages14
JournalMolecular biology of the cell
Volume13
Issue number9
DOIs
Publication statusPublished - Sep 1 2002
Externally publishedYes

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Autophagy
Vacuoles
Lysosomes
IGF Type 2 Receptor
Hepatocytes
Half-Life
Endosomes
Recycling
Enzymes
Cathepsin D
Immunoprecipitation
Pancreas
Myocardium
Electron Microscopy
Phenotype
Liver

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Eskelinen, E. L., Illert, A. L., Tanaka, Y., Schwarzmann, G., Blanz, J., Von Figura, K., & Saftig, P. (2002). Role of LAMP-2 in lysosome biogenesis and autophagy. Molecular biology of the cell, 13(9), 3355-3368. https://doi.org/10.1091/mbc.E02-02-0114

Role of LAMP-2 in lysosome biogenesis and autophagy. / Eskelinen, Eeva Liisa; Illert, Anna Lena; Tanaka, Yoshitaka; Schwarzmann, Günter; Blanz, Judith; Von Figura, Kurt; Saftig, Paul.

In: Molecular biology of the cell, Vol. 13, No. 9, 01.09.2002, p. 3355-3368.

Research output: Contribution to journalArticle

Eskelinen, EL, Illert, AL, Tanaka, Y, Schwarzmann, G, Blanz, J, Von Figura, K & Saftig, P 2002, 'Role of LAMP-2 in lysosome biogenesis and autophagy', Molecular biology of the cell, vol. 13, no. 9, pp. 3355-3368. https://doi.org/10.1091/mbc.E02-02-0114
Eskelinen EL, Illert AL, Tanaka Y, Schwarzmann G, Blanz J, Von Figura K et al. Role of LAMP-2 in lysosome biogenesis and autophagy. Molecular biology of the cell. 2002 Sep 1;13(9):3355-3368. https://doi.org/10.1091/mbc.E02-02-0114
Eskelinen, Eeva Liisa ; Illert, Anna Lena ; Tanaka, Yoshitaka ; Schwarzmann, Günter ; Blanz, Judith ; Von Figura, Kurt ; Saftig, Paul. / Role of LAMP-2 in lysosome biogenesis and autophagy. In: Molecular biology of the cell. 2002 ; Vol. 13, No. 9. pp. 3355-3368.
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