RRC ID 73636
Author Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T.
Title Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate.
Journal J Cell Sci
Abstract 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 approximately 350 kDa multimeric complex. We demonstrate that the mouse Apg12-Apg5 conjugate forms a approximately 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 approximately 800 kDa complex is expected to function in autophagosome formation, further interacting with other proteins in mammalian cells.
Volume 116(Pt 9)
Pages 1679-88
Published 2003-5-1
DOI 10.1242/jcs.00381
PMID 12665549
MeSH Amino Acid Sequence Animals Autophagy Autophagy-Related Protein 12 Autophagy-Related Proteins Base Sequence Carrier Proteins / chemistry* Carrier Proteins / genetics Carrier Proteins / metabolism* Cells, Cultured Co-Repressor Proteins DNA, Complementary / genetics HeLa Cells Histone Deacetylases Humans Intracellular Membranes / metabolism Macromolecular Substances Membrane Proteins / chemistry* Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Microscopy, Immunoelectron Molecular Sequence Data Molecular Weight Proteins / chemistry Proteins / genetics Proteins / metabolism* RNA-Binding Proteins Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Repetitive Sequences, Amino Acid Saccharomyces cerevisiae Proteins / chemistry Saccharomyces cerevisiae Proteins / metabolism Transcription Factors*
IF 4.573
Resource
DNA material p3xFLAG-CMV10-mApg16L (RDB20243)