Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation

• Published in: Nature (London) 2003-08, Vol.424 (6949), p.685-689
• Main Authors: Seydoux, Geraldine, DeRenzo, Cynthia, Reese, Kimberly J
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Bacteria; Biodegradation; Caenorhabditis elegans - cytology; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Cycle Proteins - metabolism; Cell Lineage; Cullin Proteins; Cytoplasm - metabolism; Elongin; Embryonic growth stage; Germ Cells - cytology; Germ Cells - metabolism; Humanities and Social Sciences; letter; Ligases - metabolism; Molecular Sequence Data; multidisciplinary; Plasma; Protein Binding; Proteins; RNA Interference; Science; Science (multidisciplinary); Transcription Factors - metabolism; Ubiquitin-Conjugating Enzymes; Ubiquitin-Protein Ligases
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01887

In many animals, establishment of the germ line depends on segregation of a specialized cytoplasm, or 'germ plasm', to a small number of germline precursor cells during early embryogenesis. Germ plasm asymmetry involves targeting of RNAs and proteins to a specific region of the oocyte and/or embryo. Here we demonstrate that germ plasm asymmetry also depends on degradation of germline proteins in non-germline (somatic) cells. We show that five CCCH finger proteins, components of the Caenorhabditis elegans germ plasm, are targeted for degradation by the novel CCCH-finger-binding protein ZIF-1. ZIF-1 is a SOCS-box protein that interacts with the E3 ubiquitin ligase subunit elongin C. Elongin C, the cullin CUL-2, the ring finger protein RBX-1 and the E2 ubiquitin conjugation enzyme UBC5 (also known as LET-70) are all required in vivo for CCCH finger protein degradation. Degradation is activated in somatic cells by the redundant CCCH finger proteins MEX-5 and MEX-6, which are counteracted in the germ line by the PAR-1 kinase. We propose that segregation of the germ plasm involves both stabilization of germline proteins in the germ line and cullin-dependent degradation in the soma.