GLH-1, the C. elegans P granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5.
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.
Orsborn
April M
AM
Molecular Microbiology and Immunology Department, University of Missouri, Columbia, MO 65212, USA.
Li
Wensheng
W
McEwen
Tamara J
TJ
Mizuno
Tomoaki
T
Kuzmin
Evgeny
E
Matsumoto
Kunihiro
K
Bennett
Karen L
KL
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000201:enzymology; D053487:DEAD-box RNA Helicases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000201:enzymology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
C524498:CSN-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D048031:JNK Mitogen-Activated Protein Kinases; C524496:KGB-1 protein, C elegans; C524497:GLH-1 protein, C elegans; D046988:Proteasome Endopeptidase Complex; C088269:vas protein, Drosophila; D053487:DEAD-box RNA Helicases