Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation.
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.
DeRenzo
Cynthia
C
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Reese
Kimberly J
KJ
Seydoux
Geraldine
G
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019070:Cell Lineage; D044842:Cullin Proteins; D003593:Cytoplasm / Q000378:metabolism*; D000075065:Elongin; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
C105153:CUL2 protein, human; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; C000616395:ELOC protein, human; D000075065:Elongin; C410587:MEX-5 protein, C elegans; C410589:MEX-6 protein, C elegans; D014157:Transcription Factors; C476529:ZIF-1 protein, C elegans; D044763:Ubiquitin-Conjugating Enzymes; C063110:let-70 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D008025:Ligases