CRMP/UNC-33 maintains neuronal microtubule arrays by promoting individual microtubule rescue

• DOI: 10.1016/j.cub.2024.12.030
• Publication Date: 2025-01-21T16:48:12Z
• Authors: Xing Liang; Regina Agulto; Kelsie Eichel; Caitlin Ann Taylor; Victor Alexander ...; Huichao Deng; Kassandra Ori-McK...; Kang Shen

SummaryMicrotubules (MTs) are intrinsically dynamic polymers. In neurons, staggered individual microtubules form stable, polarized acentrosomal MT arrays spanning the axon and dendrite to support long-distance intracellular transport. How the stability and polarity of these arrays are maintained when individual MTs remain highly dynamic is still an open question. Here we visualize MT arraysin vivoinC. elegansneurons with single microtubule resolution. We find that the CRMP family homolog, UNC-33, is essential for the stability and polarity of MT arrays in neurites. Inunc-33mutants, MTs exhibit dramatically reduced rescue after catastrophe, develop gaps in coverage, and lose their polarity, leading to trafficking defects. UNC-33 is stably anchored on the cortical cytoskeleton and forms patch-like structures along the dendritic shaft. These discrete and stable UNC-33 patches concentrate free tubulins and correlate with MT rescue sites.In vitro, purified UNC-33 preferentially associates with MT tips and increases MT rescue frequency. Together, we propose that UNC-33 functions as a microtubule-associated protein (MAP) to promote individual MT rescue locally. Through this activity, UNC-33 prevents the loss of individual MTs, thereby maintaining the coverage and polarity of MT arrays throughout the lifetime of neurons.