RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly
Neurons
0301 basic medicine
0303 health sciences
Paclitaxel
MAP Kinase Signaling System
MAP Kinase Kinase Kinases
Microtubules
Axons
Nerve Regeneration
3. Good health
Enzyme Activation
03 medical and health sciences
Genes, Reporter
Larva
Mutation
Neurites
Animals
Guanine Nucleotide Exchange Factors
RNA Interference
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Colchicine
Cell Shape
Mechanoreceptors
DOI:
10.1073/pnas.1410263111
Publication Date:
2014-10-30T23:28:44Z
AUTHORS (5)
ABSTRACT
Significance
Structural remodeling of neurons after insults to the nervous system includes retraction of the dysfunctional synaptic branches and growth of the primary neurites or new collateral branches. We find that genetic disruption of neuronal microtubules in
Caenorhabditis elegans
triggered structural remodeling through RHGF-1/RhoGEF, which is normally associated with and inhibited by microtubules. A conserved dual leucine zipper kinase, DLK-1, was activated by RHGF-1-dependent signaling, and activated DLK-1 was transported from distal neurite to the neuronal cell body, where it potentially altered genetic programs that enabled the destruction of injured synaptic branches and stimulated compensatory growth of the primary neurite. As microtubule, RhoGEF and DLK are conserved, the remodeling mechanisms described in this work could be a shared feature of both invertebrate and vertebrate nervous systems.
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CITATIONS (34)
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