TY - JOUR
T1 - Selective degradation of annexins by chaperone-mediated autophagy
AU - Cuervo, Ana Maria
AU - Gomes, Aldrin V.
AU - Barnes, Junor A.
AU - Dice, J. Fred
PY - 2000/10/27
Y1 - 2000/10/27
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M005655200
DO - 10.1074/jbc.M005655200
M3 - Article
C2 - 10938088
AN - SCOPUS:0034721869
SN - 0021-9258
VL - 275
SP - 33329
EP - 33335
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -