Altered Trafficking and Turnover of LAMP-1 in Pompe Disease-Affected Cells
| Autor: | Elizabeth L. Isaac, Doug A. Brooks, Peter J. Meikle, John J. Hopwood, Miao Yan, Elaine M. Ravenscroft |
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| Přispěvatelé: | Meikle, Peter J, Yan, Miao, Ravenscroft, Elaine M, Isaac, Elizabeth L, Hopwood, John J |
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Cell type Endocrinology Diabetes and Metabolism Molecular Sequence Data Biochemistry Cell Line Endocrinology Antigens CD Lysosome Internal medicine Glycogen storage disease type II Genetics medicine Extracellular Humans Amino Acid Sequence Molecular Biology Skin Membrane Glycoproteins biology Glycogen Storage Disease Type II Lysosome-Associated Membrane Glycoproteins Biological Transport Fibroblasts medicine.disease Cell biology Membrane glycoproteins medicine.anatomical_structure Membrane protein Cell culture biology.protein Lysosomes Intracellular |
| Zdroj: | Molecular Genetics and Metabolism. 66:179-188 |
| ISSN: | 1096-7192 |
| DOI: | 10.1006/mgme.1998.2800 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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