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

• DOI: 10.1073/pnas.1410263111
• Publication Date: 2014-10-30T23:28:44Z
• Authors: Chun-Hao Chen; Albert Lee; Chien-Po Liao; Ya-Wen Liu; Chun-Liang Pan
• Keywords: 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

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.