SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans

Cell. 2009 Jan 23;136(2):308-21. doi: 10.1016/j.cell.2008.12.022.

Abstract

How autophagy, an evolutionarily conserved intracellular catabolic system for bulk degradation, selectively degrades protein aggregates is poorly understood. Here, we show that several maternally derived germ P granule components are selectively eliminated by autophagy in somatic cells during C. elegans embryogenesis. The activity of sepa-1 is required for the degradation of these P granule components and for their accumulation into aggregates, termed PGL granules, in autophagy mutants. SEPA-1 forms protein aggregates and is also a preferential target of autophagy. SEPA-1 directly binds to the P granule component PGL-3 and also to the autophagy protein LGG-1/Atg8. SEPA-1 aggregates consistently colocalize with PGL granules and with LGG-1 puncta. Thus, SEPA-1 functions as a bridging molecule in mediating the specific recognition and degradation of P granule components by autophagy. Our study reveals a mechanism for preferential degradation of protein aggregates by autophagy and emphasizes the physiological significance of selective autophagy during animal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autophagy*
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoplasmic Granules / metabolism*
  • Disorders of Sex Development
  • Extrachromosomal Inheritance
  • Male
  • Molecular Sequence Data
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • PGL-3 protein, C elegans
  • RNA-Binding Proteins
  • SEPA-1 protein, C elegans

Associated data

  • GENBANK/CAB07643