ATG5 - an essential regulator of autophagosome assembly

Wed, 06/03/2015 - 15:02

Autophagy is important for the removal of damaged organelles or proteins as well as for the regulation of cellular homeostasis in response to stress. Proteins or organelles that are targeted for degradation are engulfed in a double-membrane structure called the autophagosome that eventually fuses with the lysosome to mediate cargo degradation. Atg5 plays an important regulatory role in the early steps of this process. During early autophagosome assembly Atg5 is conjugated to Atg12, an ubiquitin-like protein, and associates with Atg16. This complex of Atg5-Atg12/Atg16 forms a large multimeric complex and localizes to early autophagsome structure where it plays an essential role in the lipidation of Atg8. Atg8 is another ubiquitin-like protein that, upon lipidation, inserts into the autophagosome membrane to help recruit additional lipid components and autophagy machinery as well as cargo targeted for degradation. The Atg5-Atg12/Atg16 complex functions as an E3 ligase for the lipidation of Atg8 and is essential to autophagosome formation.

The Jahn group at the Max Planck Institute used the Atg5 antibody to characterize the interaction of Rab26 with autophagy proteins (1). They used immunoprecipitation experiments to show the GTPase Rab26, a protein associated with synaptic vesicles also interacts with Atg5 and Atg16. This indicates a potential role for Rab26 in the targeting of synaptic vesicles for degradation through autophagy. Granato et al. studied pro-survival mechanisms of bortezomib treated lymphoma cells (2). They depleted Atg 5 and used Atg5 antibody to confirm knockdown by western blot. Disrupting autophagy prevented the pro-survival effects of bortezomib suggesting co-treatment with autophagy inhibitors may be of therapeutic value. The Hooper group at UT Southwestern studied the role of autophagy in host defense against invasive bacteria in the intestine (3). They generated tissue specific Atg5 knockout mice and used the Atg5 antibody to confirm absence of protein. Their experiments showed autophagy was important for limiting infections by invasive bacteria. The Desjardin group published research in Nature Immunology autophagy enhances the presentation of viral antigens (4). They used the Atg5 antibody to confirm siRNA depletion or knockout of Atg5 and showed antigen presentation was subsequently reduced. While autophagy is important in immune response viruses, the Cirone group showed that by appropriating autophagy machinery the Epstein Barr virus (EBV) can enhance viral replication (5). They used the Atg5 antibody to confirm siRNA depletion of Atg5 by western blot to demonstrate autophagy is needed for enhanced EBV lytic gene expression.

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  2. 24086672
  3. 23768496
  4. 19305394
  5. 25142602

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