4.8 Article

RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410263111

关键词

axon retraction; axon regeneration; Rho signaling; DLK; microtubules

资金

  1. National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
  2. National BioResources Project, Japan
  3. National Science Council [NSC99-2320-B-002-080, NSC100-2320-B-002-095-MY3, NSC101-2321-B-002-071-MY3]
  4. National Taiwan University [NTU-CDP-102R7810]

向作者/读者索取更多资源

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.

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