title: A network of conserved formins, regulated by the guanine exchange factor EXC-5 and the GTPase CDC-42, modulates tubulogenesis in vivo.
abstract: The C. elegans excretory cell (EC) is a powerful model for tubulogenesis, a conserved process that requires precise cytoskeletal regulation. EXC-6, an ortholog of the disease-associated formin INF2, coordinates cell outgrowth and lumen formation during EC tubulogenesis by regulating F-actin at the tip of the growing canal and the dynamics of basolateral microtubules. EXC-6 functions in parallel with EXC-5/FGD, a predicted activator of the Rho GTPase Cdc42. Here, we identify the parallel pathway: EXC-5 functions through CDC-42 to regulate two other formins: INFT-2, another INF2 ortholog, and CYK-1, the sole ortholog of the mammalian diaphanous (mDia) family of formins. We show that INFT-2 promotes F-actin accumulation in the EC, and that CYK-1 inhibits INFT-2 to regulate F-actin levels and EXC-6-promoted outgrowth. As INF2 and mDia physically interact and cross-regulate in cultured cells, our work indicates that a conserved EXC-5-CDC-42 pathway modulates this regulatory interaction and that it is functionally important in vivo during tubulogenesis.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA shaye@uic.edu.|Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.|Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Daniel D
authors.identifier: 0000-0002-3962-6903
authors.initials: DD
authors.lastname: Shaye
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.|Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Iva
authors.initials: I
authors.lastname: Greenwald
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian; D005326:Fetal Proteins / Q000737:chemistry / Q000235:genetics*; D000080865:Formins; D019204:GTP-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D005326:Fetal Proteins; D000080865:Formins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C081779:cdc-42 protein, C elegans; C434210:exc-5 protein, C elegans; D019204:GTP-Binding Proteins
keywords: C. elegans; Cdc42; Diaphanous; FGD; INF2; Tubulogenesis