Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Carrier Proteins
  • Cell Line
  • Cytoplasm
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping

MeSH Major

  • Autophagy
  • Caveolin 1
  • Microtubule-Associated Proteins
  • Pneumocytes
  • Small Ubiquitin-Related Modifier Proteins

abstract

  • Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse environments, although the regulation of this process remains incompletely understood. We have recently observed that caveolin-1 (Cav-1), a major constituent of lipid rafts on plasma membrane, can regulate autophagy in cigarette smoking-induced injury of lung epithelium, although the underlying molecular mechanisms remain incompletely understood. In the present study we found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an ubiquitin-like conjugation system crucial for autophagosome formation, in lung epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5. Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy but resulted in decreased interactions between Cav-1 and another molecule. Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1 binding motif on ATG12 disrupted their interaction and further augmented autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy protein associating with the ATG12-ATG5 conjugate during autophagosome formation. Altogether these studies clearly demonstrate that Cav-1 competitively interacts with the ATG12-ATG5 system to suppress the formation and function of the latter in lung epithelial cells, thereby providing new insights into the molecular mechanisms by which Cav-1 regulates autophagy and suggesting the important function of Cav-1 in certain lung diseases via regulation of autophagy homeostasis. Copyright © 2014 the American Physiological Society.

publication date

  • June 1, 2014

has subject area

  • Amino Acid Sequence
  • Animals
  • Autophagy
  • Binding, Competitive
  • Carrier Proteins
  • Caveolin 1
  • Cell Line
  • Cytoplasm
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins
  • Pneumocytes
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Small Ubiquitin-Related Modifier Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00268.2013

PubMed ID

  • 24727585

Additional Document Info

start page

  • L1016

end page

  • L1025

volume

  • 306

number

  • 11