title: Tumorhead distribution to cytoplasmic membrane of neural plate cells is positively regulated by Xenopus p21-activated kinase 1 (X-PAK1).
abstract: Tumorhead (TH) regulates neural plate cell proliferation during Xenopus early development, and gain or loss of function prevents neural differentiation. TH shuttles between the nuclear and cytoplasmic/cortical cell compartments in embryonic cells. In this study, we show that subcellular distribution of TH is important for its functions. Targeting TH to the cell cortex/membrane potentiates a TH gain of function phenotype and results in neural plate expansion and inhibition of neuronal differentiation. We have found that TH subcellular localization is regulated, and that its shuttling between the nucleus and the cell cortex/cytoplasm is controlled by the catalytic activity of p21-activated kinase, X-PAK1. The phenotypes of embryos that lack, or have excess, X-PAK1 activity mimic the phenotypes induced by loss or gain of TH functions, respectively. We provide evidence that X-PAK1 is an upstream regulator of TH and discuss potential functions of TH at the cell cortex/cytoplasmic membrane and in the nucleus.
authors.affiliation: Department of Molecular Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chuan-Fen
authors.initials: CF
authors.lastname: Wu
authors.forename: Claude
authors.initials: C
authors.lastname: Delsert
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faure
authors.forename: Edwin E
authors.initials: EE
authors.lastname: Traverso
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
authors.forename: Jian
authors.initials: J
authors.lastname: Kuang
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Etkin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morin
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008959:Models, Neurological; D009154:Mutation; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases
chemical_list: D017931:DNA Primers; D029867:Xenopus Proteins; C437083:trhd protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases