title: Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis.
abstract: To gain insight into the molecular mechanisms underlying the control of morphogenetic signals by H+ flux during embryogenesis, we tested Fusicoccin-A (FC), a compound produced by the fungus Fusicoccum amygdali Del. In plant cells, FC complexes with 14-3-3 proteins to activate H+ pumping across the plasma membrane. It has long been thought that FC acts on higher plants only; here, we show that exposing frog embryos to FC during early development specifically results in randomization of the asymmetry of the left-right (LR) axis (heterotaxia). Biochemical and molecular-genetic evidence is presented that 14-3-3-family proteins are an obligate component of Xenopus FC receptors and that perturbation of 14-3-3 protein function results in heterotaxia. The subcellular localization of 14-3-3 mRNAs and proteins reveals novel cytoplasmic destinations, and a left-right asymmetry at the first cell division. Using gain-of-function and loss-of-function experiments, we show that 14-3-3E protein is likely to be an endogenous and extremely early aspect of LR patterning. These data highlight a striking conservation of signaling pathways across kingdoms, suggest common mechanisms of polarity establishment between C. elegans and vertebrate embryos, and uncover a novel entry point into the pathway of left-right asymmetry determination.
authors.affiliation: Vrije Universiteit, Faculty of Earth and Life Sciences, Department of Developmental Genetics, Section Molecular Plant Physiology and Biophysics, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Tom D
authors.initials: TD
authors.lastname: Bunney
authors.forename: Albertus H
authors.initials: AH
authors.lastname: De Boer
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology*; D006027:Glycosides / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: D048948:14-3-3 Proteins; D006027:Glycosides; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C512833:nodal1 protein, Xenopus; C007808:fusicoccin; D014446:Tyrosine 3-Monooxygenase