دورية أكاديمية
Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age
| العنوان: | Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age |
|---|---|
| المؤلفون: | Kiffin, Roberta, Kaushik, Susmita, Zeng, Mei, Bandyopadhyay, Urmi, Zhang, Cong, Massey, Ashish C., Martinez-Vicente, Marta, Cuervo, Ana Maria |
| بيانات النشر: | Company of Biologists |
| سنة النشر: | 2007 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Research Article |
| الوصف: | Rates of autophagy, the mechanism responsible for lysosomal clearance of cellular components, decrease with age. We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form of autophagy, by which particular cytosolic proteins are delivered to lysosomes after binding to the lysosome-associated membrane protein type 2A (LAMP-2A), a receptor for this pathway. Rates of CMA decrease with age because of a decrease in the levels of LAMP-2A. In this work we have investigated the reasons for the reduced levels of LAMP-2A with age. While transcriptional rates of LAMP-2A remain unchanged with age, the dynamics and stability of the receptor in the lysosomal compartment are altered. The mobilization of the lysosomal lumenal LAMP-2A to the membrane when CMA is activated is altered in lysosomes from old animals, leading to the presence of an unstable pool of lumenal LAMP-2A. By contrast, the regulated cleavage of LAMP-2A at the lysosomal membrane is reduced owing to altered association of the receptor and the protease responsible for its cleavage to particular membrane microdomain regions. We conclude that age-related changes at the lysosomal membrane are responsible for the altered turnover of the CMA receptor in old organisms and the consequent decline in this pathway. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://jcs.biologists.org/cgi/content/short/jcs.001073v1Test; http://dx.doi.org/10.1242/jcs.001073Test |
| DOI: | 10.1242/jcs.001073 |
| الإتاحة: | https://doi.org/10.1242/jcs.001073Test http://jcs.biologists.org/cgi/content/short/jcs.001073v1Test |
| حقوق: | Copyright (C) 2007, Company of Biologists |
| رقم الانضمام: | edsbas.7706C32A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1242/jcs.001073 |
|---|