The microtubule cytoskeleton plays a central role in neuron development and functioning. It serves as tracks for cargo transport and offers structural support to the axons and dendrites. Previously we identified a cortical anchoring complex that holds the microtubule cytoskeleton in place in neurons, where UNC-119 functions as a linker between the cortical UNC-44 (Ankyrin) and the microtubule binding UNC-33 (CRMP) (He et al., 2020). Whereas ankyrin proteins are well described scaffolds that connect various membrane proteins to the cortical spectrin-actin cytoskeleton, it is unclear how these interactions relate to the role of UNC-44 (Ankyrin) in maintaining the microtubule integrity. Here we used a floxed
unc-70 (beta-Spectrin) allele for loss of function studies in a tissue specific manner. Whereas neuron specific depletion did lead to a strong reduction in its binding partner UNC-44 (Ankyrin), this did not lead to major microtubule defects. However, Spectrin depletion in both the PVD neuron and surrounding hypodermis did lead to defects in microtubule cytoskeleton immobilization and polarity organization in axons and dendrites. In agreement, we found that neuron specific depletion had only mild defect on dendritic arbors of the PVD neuron, whereas when co-depleted in the hypodermis the defects were much more pronounced. We are currently investigating whether hypodermal spectrin controls neuronal adhesion proteins such as SAX-7 (NRCAM), which in turn may bind to the UNC-44 (Ankyrin) to connect to the microtubules. Altogether, we found that UNC- 70 (Spectrin) acts cell autonomously and non-autonomously to maintain the neuronal microtubule cytoskeleton.