Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice

Yoshitaka Tanaka, Gundula Guhde, Anke Suter, Eeva Liisa Eskelinen, Dieter Hartmann, Renate Lüllmann-Rauch, Paul M L Janssen, Judith Blanz, Kurt Von Figura, Paul Saftig

Research output: Contribution to journalArticle

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Abstract

Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane. Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age. The surviving mice are fertile and have an almost normal life span. Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle. In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired. Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced. These findings indicate that LAMP-2 is critical for autophagy. This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.

Original languageEnglish
Pages (from-to)902-906
Number of pages5
JournalNature
Volume406
Issue number6798
DOIs
Publication statusPublished - Aug 24 2000

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Lysosome-Associated Membrane Glycoproteins
Vacuoles
Cardiomyopathies
Protein Deficiency
Glycogen Storage Disease Type IIb
Myocardial Contraction
Autophagy
Cardiac Myocytes
Muscle Cells
Pancreas
Hepatocytes
Myocardium
Skeletal Muscle
Proteins
Spleen
Kidney
Membranes
Mortality
Liver

All Science Journal Classification (ASJC) codes

  • General

Cite this

Tanaka, Y., Guhde, G., Suter, A., Eskelinen, E. L., Hartmann, D., Lüllmann-Rauch, R., ... Saftig, P. (2000). Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice. Nature, 406(6798), 902-906. https://doi.org/10.1038/35022595

Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice. / Tanaka, Yoshitaka; Guhde, Gundula; Suter, Anke; Eskelinen, Eeva Liisa; Hartmann, Dieter; Lüllmann-Rauch, Renate; Janssen, Paul M L; Blanz, Judith; Von Figura, Kurt; Saftig, Paul.

In: Nature, Vol. 406, No. 6798, 24.08.2000, p. 902-906.

Research output: Contribution to journalArticle

Tanaka, Y, Guhde, G, Suter, A, Eskelinen, EL, Hartmann, D, Lüllmann-Rauch, R, Janssen, PML, Blanz, J, Von Figura, K & Saftig, P 2000, 'Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice', Nature, vol. 406, no. 6798, pp. 902-906. https://doi.org/10.1038/35022595
Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lüllmann-Rauch R et al. Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice. Nature. 2000 Aug 24;406(6798):902-906. https://doi.org/10.1038/35022595
Tanaka, Yoshitaka ; Guhde, Gundula ; Suter, Anke ; Eskelinen, Eeva Liisa ; Hartmann, Dieter ; Lüllmann-Rauch, Renate ; Janssen, Paul M L ; Blanz, Judith ; Von Figura, Kurt ; Saftig, Paul. / Accumulation of autophagic vacuoles and cardiomyopathy LAMP-2-deficient mice. In: Nature. 2000 ; Vol. 406, No. 6798. pp. 902-906.
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