Identification of Regulators of Chaperone-Mediated Autophagy

Urmi Bandyopadhyay, Sunandini Sridhar, Susmita Kaushik, Roberta Kiffin, Ana Maria Cuervo

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of cytosolic proteins in lysosomes that contributes to cellular quality control and becomes an additional source of amino acids when nutrients are scarce. A chaperone complex delivers CMA substrates to a receptor protein at the lysosomal membrane that assembles into multimeric translocation complexes. However, the mechanisms regulating this process remain, for the most part, unknown. In this work, we have identified two regulatory proteins, GFAP and EF1α, that mediate a previously unknown inhibitory effect of GTP on CMA. GFAP stabilizes the multimeric translocation complex against chaperone-mediated disassembly, whereas GTP-mediated release of EF1α from the lysosomal membrane promotes self-association of GFAP, disassembly of the CMA translocation complex, and the consequent decrease in CMA. The dynamic interactions of these two proteins at the lysosomal membrane unveil now a role for GTP as a negative regulator of CMA.

Original languageEnglish (US)
Pages (from-to)535-547
Number of pages13
JournalMolecular Cell
Volume39
Issue number4
DOIs
StatePublished - Aug 1 2010

Keywords

  • Cellbio
  • Cellcycle
  • Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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