title: A retinoblastoma orthologue is required for the sensing of a chalone in Dictyostelium discoideum.
abstract: Retinoblastoma-like proteins regulate cell differentiation and inhibit cell proliferation. The Dictyostelium discoideum retinoblastoma orthologue RblA affects the differentiation of cells during multicellular development, but it is unclear whether RblA has a significant effect on Dictyostelium cell proliferation, which is inhibited by the secreted proteins AprA and CfaD. We found that rblA⁻ cells in shaking culture proliferate to a higher density, die faster after reaching stationary density, and, after starvation, have a lower spore viability than wild-type cells, possibly because in shaking culture, rblA⁻ cells have both increased cytokinesis and lower extracellular accumulation of CfaD. However, rblA⁻ cells have abnormally slow proliferation on bacterial lawns. Recombinant AprA inhibits the proliferation of wild-type cells but not that of rblA⁻ cells, whereas CfaD inhibits the proliferation of both wild-type cells and rblA⁻ cells. Similar to aprA⁻ cells, rblA⁻ cells have a normal mass and protein accumulation rate on a per-nucleus basis, indicating that RblA affects cell proliferation but not cell growth. AprA also functions as a chemorepellent, and RblA is required for proper AprA chemorepellent activity despite the fact that RblA does not affect cell speed. Together, our data indicate that an autocrine proliferation-inhibiting factor acts through RblA to regulate cell density in Dictyostelium, suggesting that such factors may signal through retinoblastoma-like proteins to control the sizes of structures such as developing organs or tumors.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, USA.
authors.forename: Deenadayalan
authors.initials: D
authors.lastname: Bakthavatsalam
authors.forename: Michael J V
authors.initials: MJ
authors.lastname: White
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Herlihy
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Phillips
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D002453:Cell Cycle; D049109:Cell Proliferation; D050150:Chalones / Q000494:pharmacology*; D004023:Dictyostelium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050150:Chalones; D015800:Protozoan Proteins; D050720:Retinoblastoma-Like Protein p107