Reference - Detail
| RRC ID | 88121 |
|---|---|
| Author | Zhou J, Feng C, Sun Y, Noma K, Jin Y. |
| Title | A tubulin-MAPKKK pathway engages tubulin isotype interaction for neuroprotection. |
| Journal | Proc Natl Acad Sci U S A |
| Abstract |
The microtubule (MT) cytoskeleton is essential for neuronal morphology, neurite growth, synapse formation and maintenance, as well as regulation of signal transduction. Most cells express multiple isotypes of α- and β-tubulin that can coassemble into MTs. While a variety of signaling pathways regulate MT integrity and homeostasis, little is known about how tubulin isotypes interact in vivo. Here, we report a mechanism in which altered function of a neuronal β-tubulin in Caenorhabditis elegans activates the conserved kinase DLK-1 and its downstream signal transduction, which in turn upregulates expression of an α-tubulin isotype to ensure MT integrity. We find that alteration in the T7 loop of the β-tubulin/BEN-1 causes the formation of BEN-1-enriched islands along MTs in neurites. Combining genome editing with cellular imaging, we identified amino acid residues in α-tubulin/TBA-2 that are necessary for formation of BEN-1 islands. Activation of DLK-1 signaling in ben-1 mutants promotes TBA-2 transcription and protects axon and synapse morphology. These data uncover a positive feedback loop between DLK-1 and regulation of tubulin isotype interaction that maintains neuronal resilience. |
| Volume | 122(34) |
| Pages | e2507208122 |
| Published | 2025-8-26 |
| DOI | 10.1073/pnas.2507208122 |
| PMID | 40811477 |
| PMC | PMC12403078 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism MAP Kinase Kinase Kinases* / genetics MAP Kinase Kinase Kinases* / metabolism Microtubules / metabolism Neurites / metabolism Neurons / metabolism Neuroprotection* Signal Transduction Synapses / metabolism Tubulin* / genetics Tubulin* / metabolism |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4024 tm6948 |