title: RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly.
abstract: Neurons remodel their connectivity in response to various insults, including microtubule disruption. How neurons sense microtubule disassembly and mount remodeling responses by altering genetic programs in the soma are not well defined. Here we show that in response to microtubule disassembly, the Caenorhabditis elegans PLM neuron remodels by retracting its synaptic branch and overextending the primary neurite. This remodeling required RHGF-1, a PDZ-Rho guanine nucleotide exchange factor (PDZ-RhoGEF) that was associated with and inhibited by microtubules. Independent of the myosin light chain activation, RHGF-1 acted through Rho-dependent kinase LET-502/ROCK and activated a conserved, retrograde DLK-1 MAPK (DLK-1/dual leucine zipper kinase) pathway, which triggered synaptic branch retraction and overgrowth of the PLM neurite in a dose-dependent manner. Our data represent a neuronal remodeling paradigm during development that reshapes the neural circuit by the coordinated removal of the dysfunctional synaptic branch compartment and compensatory extension of the primary neurite.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, and.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Albert
authors.initials: A
authors.lastname: Lee
authors.affiliation: Institute of Molecular Medicine, College of Medicine, and.
authors.forename: Chien-Po
authors.initials: CP
authors.lastname: Liao
authors.affiliation: Institute of Molecular Medicine, College of Medicine, and.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Institute of Molecular Medicine, College of Medicine, and chunliangpan@gmail.com.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Pan
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D048430:Cell Shape; D003078:Colchicine / Q000494:pharmacology; D004789:Enzyme Activation; D017930:Genes, Reporter; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D007814:Larva; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology* / Q000648:ultrastructure; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014110:Touch / Q000502:physiology; D014404:Tubulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050257:Tubulin Modulators / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D020662:Guanine Nucleotide Exchange Factors; C118234:MEC-12 protein, C elegans; C115872:Mec-7 protein, C elegans; C516804:RHGF-1 protein, C elegans; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D050257:Tubulin Modulators; C515856:LET-502 protein, C elegans; D054460:rho-Associated Kinases; C498050:DLK-1 protein, C elegans; D020930:MAP Kinase Kinase Kinases; D017239:Paclitaxel; D003078:Colchicine
keywords: DLK; Rho signaling; axon regeneration; axon retraction; microtubules