Cited by 1,394Autophagy in Disease and TherapyUbiquitin and proteasome pathwaysCellular transport and secretion

LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation

Kabeya, Yukiko, Mizushima, Noboru, Yamamoto, Akitsugu, Oshitani-Okamoto, Satsuki, Ohsumi, Yoshinori, Yoshimori, Tamotsu·2004·Journal of Cell Science

Abstract

Rat LC3, a homologue of yeast Atg8 (Aut7/Apg8), localizes to autophagosomal membranes after post-translational modifications. The C-terminal fragment of LC3 is cleaved immediately following synthesis to yield a cytosolic form called LC3-I. A subpopulation of LC3-I is further converted to an autophagosome-associating form, LC3-II. Because yeast Atg8 is conjugated with phosphatidylethanolamine (PE) by a ubiquitin-like system, it has been hypothesized that LC3 is modified in a similar manner. Here, we show that [(14)C]-ethanolamine was preferentially incorporated into LC3-II, suggesting that LC3-II is a PE-conjugated form. LC3-II can be a substrate of mammalian Atg4B, a homologue of yeast Atg8-PE deconjugase, supporting the idea that LC3-II is LC3-PE. Moreover, two other mammalian homologues of yeast Atg8, gamma-aminobutyric-acid-type-A-receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE16) also generate form II, which are recovered in membrane fractions. Generation of the form II correlates with autophagosome association of GABARAP and GATE16. These results suggest that all mammalian Atg8 homologues receive a common modification to associate with autophagosomal membrane as the form II.

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Crossref · 10.1242/jcs.01131

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Authors
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., & Yoshimori, T.
Affiliations
  • National Institute for Basic Biology (JP)
  • Nagahama Institute of Bio-Science and Technology (JP)
  • National Institute of Genetics (JP)
Corresponding author
Yoshimori, Tamotsu
Venue
Journal of Cell Science
Published
2004-06-01
Volume
117
Issue
13
Pages
2805-2812
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W2068153705
Cited by
1,394
References
29
Citations by year
2026: 22 · 2025: 40 · 2024: 49 · 2023: 72 · 2022: 67 · 2021: 100 · 2020: 89 · 2019: 86 · 2018: 77 · 2017: 74 · 2016: 83 · 2015: 99 · 2014: 76 · 2013: 85 · 2012: 97
FWCI
18.45
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
LC3, GABARAP, autophagosomal membrane, LC3-II, phosphatidylethanolamine conjugation, ATG4B, autophagosomes, protein localization, ethanolamine incorporation
MeSH terms
Autophagy-Related Protein 8 Family, Animals, Carbon Radioisotopes, Carrier Proteins, Fluorescent Dyes, Glycine, HeLa Cells, Humans, Kinetics, Lysosomes, Microfilament Proteins, Microscopy, Fluorescence, Microtubule-Associated Proteins, Phagosomes, Precipitin Tests, Saccharomyces cerevisiae, Stem Cells, Subcellular Fractions, Substrate Specificity, Teratocarcinoma, Ethanolamine, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Luminescent Agents, Apoptosis Regulatory Proteins, Mice

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