Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy.
The lysosomal membrane proteins LAMP-1 and LAMP-2 are estimated to contribute to about 50% of all proteins of the lysosome membrane. Surprisingly, mice deficient in either LAMP-1 or LAMP-2 are viable and fertile. However, mice deficient in both LAMP-1 and LAMP-2 have an embryonic lethal phenotype. These results show that these two major lysosomal membrane proteins share common functions in vivo. However, LAMP-2 seems to have more specific functions since LAMP-2 single deficiency has more severe consequences than LAMP-1 single deficiency. Mutations in LAMP-2 gene cause a lysosomal glycogen storage disease, Danon disease, in humans. LAMP-2 deficient mice replicate the symptoms found in Danon patients including accumulation of autophagic vacuoles in heart and skeletal muscle. In embryonic fibroblasts, mutual disruption of both LAMPs is associated with an increased accumulation of autophagic vacuoles and unesterified cholesterol, while protein degradation rates are not affected. These results clearly show that the LAMP proteins fulfil functions far beyond the initially suggested roles in maintaining the structural integrity of the lysosomal compartment.
Eskelinen
Eeva-Liisa
EL
Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Viikinkaari 5D, 00014 Helsinki, Finland. eeva-liisa.eskelinen@helsinki.fi
D000818:Animals; D001343:Autophagy; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D001678:Organelle Biogenesis; D010641:Phenotype
D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2