Antagonistic Relationship Between Microtubule‐Stabilizing and Destabilizing Factors for the Maintenance of Axonal Microtubule Dynamics and Polarity in <scp> <i>C. elegans</i> </scp> Touch Neuron

ABSTRACT Proper regulation of microtubule (MT) cytoskeleton forms the basis for molecular and functional polarization of neurons. The optimal growth of mechanosensory neurons in C. elegans depends on the activity of the microtubule depolymerizing enzyme, Kinesin‐13/KLP‐7. Yet it's unclear how KLP‐7 collaborates with other microtubule regulators in neurons for proper MT regulation. Using the ectopic growth of mechanosensory neurons in klp‐7 mutants as a phenotypic handle , we characterized its genetic interactions with known microtubule stabilizers. We found that mutations in unc‐33 (CRMP‐2), unc‐44 (Ankyrin), or components of the unc‐14/unc‐51/vab‐8 pathway suppress klp‐7(0) ectopic growth. Quantification of EBP‐2::GFP dynamics revealed that these factors promote microtubule stability in axon‐like PLM anterior neurites, suggesting an antagonistic role to KLP‐7. Additionally, mec‐7 (β‐tubulin), unc‐33 , and unc‐44 proteins promote the plus‐end‐out microtubule polarity in these neurites, and their loss in klp‐7(0) mutant can reciprocally suppress the microtubule dynamics defects observed in single mutants. Notably, the simultaneous loss of klp‐7 and mec‐7 restored steady‐state microtubule dynamics and wild‐type‐like PLM morphology. Together, our findings suggest that the antagonistic interplay between microtubule depolymerizing kinesin KLP‐7 and microtubule‐stabilizing factors, UNC‐44, UNC‐33, and tubulins, is necessary to maintain steady‐state microtubule dynamics and plus‐end‐out axonal microtubule polarity in neurons.