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|Title:||Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells|
|Citation:||Molecular Genetics and Metabolism, 1999; 66(3):179-188|
|Publisher:||ACADEMIC PRESS INC|
|Abstract:||The lysosome-associated membrane protein (LAMP-1) is elevated in the cells and plasma from lysosomal storage disorder-affected individuals; however, the mechanism of this elevation is not well defined. In this study we have investigated the synthesis, glycoprocessing, trafficking, and turnover of LAMP-1 in human skin fibroblasts from Pompe disease patients and control individuals. There were similar levels of LAMP-1 synthesis in both cell types, but glycoprocessing was retarded in Pompe (T1/2 = 25 min) compared to control (T1/2 = 17 min) fibroblasts. There was also a marked delay in trafficking of LAMP-1 to lysosomes of Pompe (T1/2 = 200 min) compared to control (T1/2 = 100 min) cells. A proportion of newly synthesized LAMP-1 (5.4% in Pompe and 8.5% in controls) was trafficked out of the cell (T1/2 = 3.5 h in controls) and, although significantly smaller than the lysosomal form, still had a transmembrane domain and cytoplasmic tail. In contrast, a soluble lysosomal pool of LAMP-1 had no tail sequence, suggesting that it had been clipped from the membrane. In turnover studies, LAMP-1 was more stable in Pompe (T1/2 = 4.9 days) compared to control (T1/2 = 1. 6 days) cells, implying either reduced proteolysis or lysosomal function, in Pompe cells. These results indicate altered traffic and turnover of LAMP-1 in storage disorders and identify different intracellular and extracellular pools of soluble LAMP-1, suggesting alternative trafficking pathways.|
|Keywords:||Cell Line; Lysosomes; Fibroblasts; Skin; Humans; Glycogen Storage Disease Type II; Membrane Glycoproteins; Antigens, CD; Amino Acid Sequence; Biological Transport; Molecular Sequence Data; Lysosome-Associated Membrane Glycoproteins|
|Appears in Collections:||Paediatrics publications|
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