التفاصيل البيبلوغرافية
| العنوان: |
Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. |
| المؤلفون: |
Kiffin, Roberta, Kaushik, Susmita, Mei Zeng, Bandyopadhyay, Urmi, Cong Zhang, Massey, Ashish C., Martinez-Vicente, Marta, Cuervo, Ana Maria |
| المصدر: |
Journal of Cell Science; 3/1/2007, Vol. 120 Issue 5, p8-8, 1p |
| مصطلحات موضوعية: |
CELLULAR aging, LYSOSOMES, MEMBRANE proteins, CELL receptors, PROTEOLYTIC enzymes |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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