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bioRxiv · 10.64898/2026.09.14.751438

Spatially Confined Phase Separation Promotes Local Tubulin Availability to Stabilize Ciliary Microtubule Growth

XU, K.·Zhu, Z.·Chai, Y.·Li, W.·Ou, G.
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Abstract

How microtubule (MT) growth is locally sustained within cilia remains a central unanswered question in ciliogenesis. Here we identify RAT-1 as a regulator of ciliary tubulin homeostasis and MT growth. Genetic screens in Caenorhabditis elegans show that loss of RAT-1 suppresses the toxic effects of a mutant -tubulin and restores ciliary structure, while RAT-1 deficiency reduces tubulin turnover at the ciliary tip, indicating its physiological role in tuning ciliary MT dynamics. Mechanistically, RAT-1 forms intra-ciliary condensates selectively at the distal region through an auto-inhibitory -helix and phosphorylation by the distally localized ciliary kinase. RAT-1 enriches tubulin within condensates in vivo/vitro, and cooperates with end-binding proteins to facilitate sustained MT growth in vitro. Notably, heterologous expression of worm RAT-1 reveals conserved condensate behavior within mammalian cilia. Our findings reveal a kinase-regulated mechanism controlling RAT-1 condensation within cilia and establish RAT-1 as a regulator of ciliary MT dynamics.

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XU, K., Zhu, Z., Chai, Y., Li, W., Ou, G.. 2026-09-18. Spatially Confined Phase Separation Promotes Local Tubulin Availability to Stabilize Ciliary Microtubule Growth. https://doi.org/10.64898/2026.09.14.751438

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