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First published online 15 August 2007
doi: 10.1242/dev.005181


Development 134, 3383-3392 (2007)
Published by The Company of Biologists 2007


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GLH-1, the C. elegans P granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5

April M. Orsborn1,*, Wensheng Li1,{dagger}, Tamara J. McEwen1, Tomoaki Mizuno2, Evgeny Kuzmin1, Kunihiro Matsumoto2 and Karen L. Bennett1,{ddagger}

1 Molecular Microbiology and Immunology Department, University of Missouri, Columbia, MO 65212, USA.
2 Molecular Biology Department, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan.

{ddagger} Author for correspondence (e-mail: bennettk{at}missouri.edu)

Accepted 2 June 2007

The GLHs (germline RNA helicases) are constitutive components of the germline-specific P granules in the nematode Caenorhabditis elegans and are essential for fertility, yet how GLH proteins are regulated remains unknown. KGB-1 and CSN-5 are both GLH binding partners, previously identified by two-hybrid interactions. KGB-1 is a MAP kinase in the Jun N-terminal kinase (JNK) subfamily, whereas CSN-5 is a subunit of the COP9 signalosome. Intriguingly, although loss of either KGB-1 or CSN-5 results in sterility, their phenotypes are strikingly different. Whereas csn-5 RNA interference (RNAi) results in under-proliferated germlines, similar to glh-1/glh-4(RNAi), the kgb-1(um3) loss-of-function mutant exhibits germline over-proliferation. When kgb-1(um3) mutants are compared with wild-type C. elegans, GLH-1 protein levels are as much as 6-fold elevated and the organization of GLH-1 in P granules is grossly disrupted. A series of additional in vivo and in vitro tests indicates that KGB-1 and CSN-5 regulate GLH-1 levels, with GLH-1 targeted for proteosomal degradation by KGB-1 and stabilized by CSN-5. We propose the `good cop: bad cop' team of CSN-5 and KGB-1 imposes a balance on GLH-1 levels, resulting in germline homeostasis. In addition, both KGB-1 and CSN-5 bind Vasa, a Drosophila germ granule component; therefore, similar regulatory mechanisms might be conserved from worms to flies.

Key words: Germline, MAPK docking site, Signalosome, Degradation, Phosphodegron, Vasa, Homeostasis


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