期刊
EMBO JOURNAL
卷 22, 期 1, 页码 47-59出版社
WILEY
DOI: 10.1093/emboj/cdg002
关键词
autophagy; galactosialidosis; lysosomes; proteases; protein degradation
资金
- NIA NIH HHS [AG06116, R01 AG006116, R37 AG006116, AG00829] Funding Source: Medline
- NIDDK NIH HHS [R01 DK052025, DK52025] Funding Source: Medline
Protective protein/cathepsin A (PPCA) has a serine carboxypeptidase activity of unknown physiological function. We now demonstrate that this protease activity triggers the degradation of the lysosome-associated membrane protein type 2a (lamp2a), a receptor for chaperone-mediated autophagy (CMA). Degradation of lamp2a is important because its level in the lysosomal membrane is a rate-limiting step of CMA. Cells defective in PPCA show reduced rates of lamp2a degradation, higher levels of lamp2a and higher rates of CMA. Restoration of PPCA protease activity increases rates of lamp2a degradation, reduces levels of lysosomal lamp2a and reduces rates of CMA. PPCA associates with lamp2a on the lysosomal membrane and cleaves lamp2a near the boundary between the luminal and transmembrane domains. In addition to the well-studied role of PPCA in targeting and protecting two lysosomal glycosidases, we have defined a role for the proteolytic activity of this multifunctional protein.
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