LC3B is indispensable for selective autophagy of p62 but not basal autophagy

Biochem Biophys Res Commun. 2014 Mar 28;446(1):309-15. doi: 10.1016/j.bbrc.2014.02.093. Epub 2014 Feb 28.

Abstract

Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.

Keywords: Autophagy; GABARAP; LC3; p62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • Autophagy-Related Protein 8 Family
  • Cells, Cultured
  • HEK293 Cells
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / physiology
  • Humans
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology*
  • Models, Molecular
  • RNA, Small Interfering / genetics
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequestosome-1 Protein
  • Static Electricity

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Protein 8 Family
  • GABARAP protein, human
  • GABARAPL1 protein, human
  • GABARAPL2 protein, human
  • Heat-Shock Proteins
  • MAP1LC3B protein, human
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse