期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 46, 页码 16568-16573出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410263111
关键词
axon retraction; axon regeneration; Rho signaling; DLK; microtubules
资金
- National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
- National BioResources Project, Japan
- National Science Council [NSC99-2320-B-002-080, NSC100-2320-B-002-095-MY3, NSC101-2321-B-002-071-MY3]
- National Taiwan University [NTU-CDP-102R7810]
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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