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doi: 10.1242/10.1242/jcs.00381
Research Article |
1 PRESTO, Japan Science and Technology Corporation, Kawaguchi 332-0012,
Japan
2 Department of Cell Biology, National Institute for Basic Biology, 38
Nishigonaka, Myodaiji, Okazaki 444-8585, Japan
3 Department of Molecular Biomechanics, School of Life Science, The Graduate
University for Advanced Studies, Okazaki 444-8585, Japan
4 Department of Physiology, Kansai Medical University, Moriguchi 570-8506,
Japan
5 Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka
565-0871, Japan
6 National Institute of Advanced Industrial Science and Technology, Tokyo
135-0064, Japan
7 Department of Cell Genetics, National Institute of Genetics, Mishima 411-8540,
Japan
* Authors for correspondence (e-mail: nmizu{at}nibb.ac.jp; yohsumi{at}nibb.ac.jp)
Accepted 21 January 2003
Macroautophagy is the major intracellular degradation system delivering
cytoplasmic components to the lysosome/vacuole. We have shown that, in yeast
and mammalian cells, the Apg12-Apg5 protein conjugate, which is formed by a
ubiquitin-like system, is essential for autophagosome formation. In yeast, the
Apg12-Apg5 conjugate interacts with a small coiled-coil protein, Apg16, to
form a 
350 kDa multimeric complex. We demonstrate that the mouse
Apg12-Apg5 conjugate forms a 800 kDa protein complex containing a novel
WD-repeat protein. Because the N-terminal region of this novel protein shows
homology with yeast Apg16, we have designated it mouse Apg16-like protein
(Apg16L). Apg16L, however, has a large C-terminal domain containing seven WD
repeats that is absent from yeast Apg16. Apg16L interacts with both Apg5 and
additional Apg16L monomers; neither interaction, however, depends on the
WD-repeat domain. In conjunction with Apg12-Apg5, Apg16L associates with the
autophagic isolation membrane for the duration of autophagosome formation.
Because these features are similar to yeast Apg16, we concluded Apg16L is the
functional counterpart of the yeast Apg16. We also found that membrane
targeting of Apg16L requires Apg5 but not Apg12. Because WD-repeat proteins
provide a platform for protein-protein interactions, the 800 kDa complex
is expected to function in autophagosome formation, further interacting with
other proteins in mammalian cells.
Key words: Autophagy, Apg12, Apg5, WD repeat
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