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Lysosomal Membrane Proteins

  • Chapter
Lysosomes

Part of the book series: Medical Intelligence Unit ((MIUN))

Abstract

The lysosomal limiting membrane has multiple functions including acidification of the lysosomal matrix, sequestration of lysosomal enzymes, mediation of fusion events beween lysosomes and other organelles, and transport of degradation products to the cytoplasm. Lysosomal membrane proteins are usually highly glycosylated proteins decorating the luminal surface of lysosomal membranes. LAMP-1, LAMP-2 and LIMP-2 are the most abundant components of this membrane. Experiments on knockout mice have demonstrated that these proteins are important for normal cell physiology and that they can be involved in pathological conditions. The deficiency of LAMP-1 causes only a mild phenotype and also no apparent lysosomal dysfunctions. It is likely that the lack of LAMP-1 may be compensated by the structurally related LAMP-2. A role for LAMP-2 in the so-called chaperone-mediated autophagy has been described. Furthermore, LAMP-2 deficiency in mice has revealed roles in lysosomal enzyme targeting, autophagy and lysosomal biogenesis. LAMP-2-deficient mice exhibit a similar phenotype to individuals with Danon disease, which is caused by mutations in the LAMP-2 gene. Experiments on LIMP-2 knockout mice and overexpression studies also suggested specific functions for this protein in maintaining normal lysosomal biogenesis. Apart from the major proteins of the lysosomal membrane, about 20 less abundant or transient components of this membrane have been described. Although it is known that mutations in some of these proteins are associated with human disease, for most of the lysosomal membrane components the actual function is yet to be determined.

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  1. Biochemisches Institut, Christian-Albrechts-Universität Kiel, Olshausenstr. 40, 24098, Kiel, Germany

    Paul Saftig

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Saftig, P. (2005). Lysosomal Membrane Proteins. In: Lysosomes. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28957-7_4

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