A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice
Tekijät: Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lullmann-Rauch R, Janssen PML, Blanz J, von Figura K, Saftig P
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2000
Journal: Nature
Tietokannassa oleva lehden nimi: NATURE
Lehden akronyymi: NATURE
Vuosikerta: 406
Numero: 6798
Aloitussivu: 902
Lopetussivu: 906
Sivujen määrä: 6
ISSN: 0028-0836
DOI: https://doi.org/10.1038/35022595
Tiivistelmä
Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane(1-7). 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(8) causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.
Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane(1-7). 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(8) causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.
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