Cathepsin a regulates chaperone-mediated autophagy through cleavage of the lysosomal receptor

Ana Maria Cuervo, Linda Mann, Erik J. Bonten, Alessandra D'Azzo, J. Fred Dice

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)47-59
Number of pages13
JournalEMBO Journal
Volume22
Issue number1
DOIs
StatePublished - Jan 2 2003

Fingerprint

Lysosome-Associated Membrane Glycoproteins
Cathepsins
Autophagy
Cathepsin A
Degradation
Proteins
Proteolysis
Peptide Hydrolases
Membranes
Glycoside Hydrolases
Restoration

Keywords

  • Autophagy
  • Galactosialidosis
  • Lysosomes
  • Proteases
  • Protein degradation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Cathepsin a regulates chaperone-mediated autophagy through cleavage of the lysosomal receptor. / Cuervo, Ana Maria; Mann, Linda; Bonten, Erik J.; D'Azzo, Alessandra; Dice, J. Fred.

In: EMBO Journal, Vol. 22, No. 1, 02.01.2003, p. 47-59.

Research output: Contribution to journalArticle

Cuervo, Ana Maria ; Mann, Linda ; Bonten, Erik J. ; D'Azzo, Alessandra ; Dice, J. Fred. / Cathepsin a regulates chaperone-mediated autophagy through cleavage of the lysosomal receptor. In: EMBO Journal. 2003 ; Vol. 22, No. 1. pp. 47-59.
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