RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly.
Proc Natl Acad Sci U S A
; 111(46): 16568-73, 2014 Nov 18.
Article
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| MEDLINE
| ID: mdl-25359212
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.
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Banco de datos:
MEDLINE
Asunto principal:
Caenorhabditis elegans
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Quinasas Quinasa Quinasa PAM
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Factores de Intercambio de Guanina Nucleótido
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Proteínas de Caenorhabditis elegans
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Mecanorreceptores
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Microtúbulos
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Regeneración Nerviosa
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Neuronas
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Animals
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Año:
2014
Tipo del documento:
Article