LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans.
Caenorhabditis elegans germline cells are maintained in an undifferentiated and mitotically dividing state by Notch signaling and the FBF (for fem-3 binding factor) RNA-binding protein. Here, we report that the LIP-1 phosphatase, a proposed homolog of mitogen-activated protein (MAP) kinase phosphatases, is required for the normal extent of germline proliferation, and that lip-1 controls germline proliferation by regulating MAP kinase activity. In wild-type germ lines, LIP-1 protein is present in the proximal third of the mitotic region, consistent with its effect on germline proliferation. We provide evidence that lip-1 expression in the germline mitotic region is controlled by a combination of GLP-1/Notch signaling and FBF repression. Unexpectedly, FBF controls the accumulation of lip-1 mRNA, and therefore is likely to control its stability or 3'-end formation. In a sensitized mutant background, LIP-1 can function as a pivotal regulator of the decision between proliferation and differentiation. The control of germline proliferation by LIP-1 has intriguing parallels with the control of stem cells and progenitor cells in vertebrates.
Lee
Myon-Hee
MH
Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA.
Hook
Brad
B
Lamont
Liana B
LB
Wickens
Marvin
M
Kimble
Judith
J
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000201:enzymology / Q000254:growth & development*; D019950:Mitogen-Activated Protein Kinase 1; D008938:Mitosis; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology; D014157:Transcription Factors
D020413:3' Untranslated Regions; D000906:Antibodies; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C409224:SEL-8 protein, C elegans; D015534:Trans-Activators; D014157:Transcription Factors; C109286:fem-3-binding protein, C elegans; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; C421904:lip-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases