RRC ID 34748
著者 Chen CH, Lee A, Liao CP, Liu YW, Pan CL.
タイトル RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 111(46)
ページ 16568-73
公開日 2014-11-18
DOI 10.1073/pnas.1410263111
PII 1410263111
PMID 25359212
PMC PMC4246272
MeSH Animals Axons / ultrastructure Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Shape Colchicine / pharmacology Enzyme Activation Genes, Reporter Guanine Nucleotide Exchange Factors / physiology* Larva MAP Kinase Kinase Kinases / physiology* MAP Kinase Signaling System / physiology Mechanoreceptors / physiology* Mechanoreceptors / ultrastructure Microtubules / drug effects Microtubules / metabolism* Microtubules / ultrastructure Mutation Nerve Regeneration / physiology* Neurites / metabolism Neurites / ultrastructure Neurons / physiology* Neurons / ultrastructure Paclitaxel / pharmacology RNA Interference Recombinant Fusion Proteins / metabolism Touch / physiology Tubulin / deficiency Tubulin / genetics Tubulin / physiology Tubulin Modulators / pharmacology rho-Associated Kinases / physiology
IF 9.412
引用数 16
WOS 分野 NEUROSCIENCES
リソース情報
線虫 mec-15(tm2691) mec-12(tm5083) cebp-1(tm2807)