title: At the acidic edge: emerging functions for lysosomal membrane proteins.
abstract: It has recently become clear that lysosomes have more complex functions than simply being the end-point on a degradative pathway. Similarly, it is now emerging that there are interesting functions for the limiting membranes around these organelles and their associated proteins. Although it has been known for several decades that the lysosomal membrane contains several highly N-glycosylated proteins, including the lysosome-associated membrane proteins LAMP-1 and LAMP-2 and lysosomal integral membrane protein-2/lysosomal membrane glycoprotein-85 (LIMP-2/LGP85), specific functions of these proteins have only recently begun to be recognized. Although the normal functions of LAMP-1 can be substituted by the structurally related LAMP-2, LAMP-2 itself has more specific tasks. Knockout of LAMP-2 in mice has revealed roles for LAMP-2 in lysosomal enzyme targeting, autophagy and lysosomal biogenesis. LAMP-2 deficiency in humans leads to Danon disease, a fatal cardiomyopathy and myopathy. Furthermore, there is evidence that LAMP-2 functions in chaperone-mediated autophagy. LIMP-2/LGP85 also seems to have specific functions in maintaining endosomal transport and lysosomal biogenesis. The pivotal function of lysosomal membrane proteins is also highlighted by the recent identification of disease-causing mutations in cystine and sialic acid transporter proteins, leading to nephropathic cystinosis and Salla disease.
authors.affiliation: Department of Biochemistry, University of Kiel, Eduard-Buchner-Haus, Olshausenstrasse 40, D-24098 Kiel, Germany.
authors.forename: Eeva-Liisa
authors.initials: EL
authors.lastname: Eskelinen
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D003554:Cystinosis / Q000235:genetics; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051116:Receptors, Scavenger; D029461:Sialic Acid Storage Disease / Q000235:genetics; D012795:Sialoglycoproteins
chemical_list: D015703:Antigens, CD; D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D012795:Sialoglycoproteins