epg-1 functions in autophagy-regulated processes and may encode a highly divergent Atg13 homolog in C. elegans

Autophagy is an evolutionarily conserved intracellular catabolic system for degradation of long-lived proteins or damaged organelles. In this study, we have identified and characterized a new gene, epg-1, that plays a role in the autophagy pathway in C. elegans. Loss of function of epg-1 causes defects in various autophagy-regulated processes, including degradation of aggregate-prone proteins and optimal survival of animals during starvation. epg-1 encodes a novel protein that shows limited sequence similarity to the yeast autophagy protein Atg13. epg-1 displays a similar expression pattern to, and directly interacts with, the C. elegans Atg1 homolog UNC-51, suggesting that epg-1 encodes a divergent functional homolog of Atg13 in C. elegans.

[1]  Yu Zhao,et al.  SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans , 2009, Cell.

[2]  S. Tooze,et al.  Kinase-Inactivated ULK Proteins Inhibit Autophagy via Their Conserved C-Terminal Domains Using an Atg13-Independent Mechanism , 2008, Molecular and Cellular Biology.

[3]  J. Guan,et al.  FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells , 2008, The Journal of cell biology.

[4]  N. Nukina,et al.  Genetic impairment of autophagy intensifies expanded polyglutamine toxicity in Caenorhabditis elegans. , 2008, Biochemical and biophysical research communications.

[5]  A. van der Vaart,et al.  A Picky Eater: Exploring the Mechanisms of Selective Autophagy in Human Pathologies , 2008, Traffic.

[6]  T. Vellai,et al.  Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans , 2008, Autophagy.

[7]  D. Klionsky,et al.  The Atg1 kinase complex is involved in the regulation of protein recruitment to initiate sequestering vesicle formation for nonspecific autophagy in Saccharomyces cerevisiae. , 2007, Molecular biology of the cell.

[8]  Nektarios Tavernarakis,et al.  Autophagy is required for necrotic cell death in Caenorhabditis elegans , 2008, Cell Death and Differentiation.

[9]  L. Avery,et al.  Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. , 2007, Genes & development.

[10]  T. Vellai,et al.  Autophagy Genes unc-51 and bec-1 Are Required for Normal Cell Size in Caenorhabditis elegans , 2007, Genetics.

[11]  M. Matsui,et al.  LC3, an Autophagosome Marker, Can be Incorporated into Protein Aggregates Independent of Autophagy: Caution in the Interpretation of LC3 Localization , 2007, Autophagy.

[12]  T. Vellai,et al.  Influence of autophagy genes on ion-channel-dependent neuronal degeneration in Caenorhabditis elegans , 2007, Journal of Cell Science.

[13]  Y. Ohsumi,et al.  Hierarchy of Atg proteins in pre‐autophagosomal structure organization , 2007, Genes to cells : devoted to molecular & cellular mechanisms.

[14]  A. Hart,et al.  Autophagy Genes Protect Against Disease Caused by Polyglutamine Expansion Proteins in Caenorhabditis elegans , 2007, Autophagy.

[15]  J. Lippincott-Schwartz,et al.  Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes , 2006, Journal of Cell Science.

[16]  Daniel J Klionsky,et al.  Development by self-digestion: molecular mechanisms and biological functions of autophagy. , 2004, Developmental cell.

[17]  D. Klionsky,et al.  The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. , 2004, Developmental cell.

[18]  D. Hall,et al.  Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans , 2003, Science.

[19]  K Suzuki,et al.  The pre‐autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation , 2001, The EMBO journal.

[20]  Kazuya Nagano,et al.  Tor-Mediated Induction of Autophagy via an Apg1 Protein Kinase Complex , 2000, The Journal of cell biology.

[21]  Yoshiaki Kamada,et al.  Apg13p and Vac8p Are Part of a Complex of Phosphoproteins That Are Required for Cytoplasm to Vacuole Targeting* , 2000, The Journal of Biological Chemistry.

[22]  Y. Ohshima,et al.  The UNC-14 protein required for axonal elongation and guidance in Caenorhabditis elegans interacts with the serine/threonine kinase UNC-51. , 1997, Genes & development.

[23]  I. Mori,et al.  Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase. , 1994, Genes & development.