Selective degradation of annexins by chaperone-mediated autophagy

Ana Maria Cuervo, Aldrin V. Gomes, Junor A. Barnes, J. Fred Dice

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Annexins are a family of proteins that bind phospholipids in a calcium-dependent manner. Analysis of the sequences of the different members of the annexin family revealed the presence of a pentapeptide biochemically related to KFERQ in some annexins but not in others. Such sequences have been proposed to be a targeting sequence for chaperone-mediated autophagy, a lysosomal pathway of protein degradation that is activated in confluent cells in response to removal of serum growth factors. We demonstrate that annexins II and VI, which contain KFERQ-like sequences, are degraded more rapidly in response to serum withdrawal, while annexins V and XI, without such sequences, are degraded at the same rate in the presence and absence of serum. Using isolated lysosomes, only the annexins containing KFERQ-like sequences are degraded by chaperone mediated-autophagy. Annexins V and XI could associate with lysosomes but did not enter the lysosomes and were not proteolytic substrates. Furthermore, four annexins containing KFERQ-like sequences, annexins I, II, IV, and VI, are enriched in lysosomes with high chaperone-mediated autophagy activity as expected for substrafe proteins. These results provide striking evidence for the importance of KFERQ motifs in substrates of chaperone-mediated autophagy.

Original languageEnglish (US)
Pages (from-to)33329-33335
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number43
DOIs
StatePublished - Oct 27 2000
Externally publishedYes

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Annexins
Autophagy
Degradation
Lysosomes
Annexin A2
Annexin A5
Annexin A6
Serum
Annexin A1
Proteins
Substrates
Proteolysis
Sequence Analysis
Phospholipids
Intercellular Signaling Peptides and Proteins
Calcium

ASJC Scopus subject areas

  • Biochemistry

Cite this

Selective degradation of annexins by chaperone-mediated autophagy. / Cuervo, Ana Maria; Gomes, Aldrin V.; Barnes, Junor A.; Dice, J. Fred.

In: Journal of Biological Chemistry, Vol. 275, No. 43, 27.10.2000, p. 33329-33335.

Research output: Contribution to journalArticle

Cuervo, Ana Maria ; Gomes, Aldrin V. ; Barnes, Junor A. ; Dice, J. Fred. / Selective degradation of annexins by chaperone-mediated autophagy. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 43. pp. 33329-33335.
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