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

Abstract

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 embryogenesis1. Germ plasm asymmetry involves targeting of RNAs and proteins to a specific region of the oocyte and/or embryo2. 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.

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Figure 1: ZIF-1 interacts with CCCH fingers targeted for degradation.
Figure 2: Depletion of ZIF-1 blocks degradation of CCCH finger proteins in somatic cells, but does not affect other soma–germline asymmetries.
Figure 3: ZIF-1 is a SOCS-box protein.
Figure 4: ZIF-1 may function as a substrate-recruitment factor for an elongin C/CUL-2 E3 ubiquitin ligase.
Figure 5: PAR-1 inhibits, and MEX-5 and MEX-6 activate, ZIF-1-dependent degradation.

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Acknowledgements

We dedicate this study to the memory of D. Nathans. We thank E. Kipreos for critical reading of the manuscript; Z. Zhao and B. Horvitz for the yeast two-hybrid library; Y. Kohara for the POS-1 antibody; B. Aman and J. Berg for many discussions about CCCH fingers; and A. Cuenca for help with the movies. This work was supported by a NIH grant and by the Steve and Michelle Kirsch Foundation.

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Correspondence to Geraldine Seydoux.

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DeRenzo, C., Reese, K. & Seydoux, G. Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation. Nature 424, 685–689 (2003). https://doi.org/10.1038/nature01887

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