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PreprintCC BYbioRxiv

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

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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BibTeX
@misc{k2026spatially,
  title = {{Spatially Confined Phase Separation Promotes Local Tubulin Availability to Stabilize Ciliary Microtubule Growth}},
  author = {K. XU and Z. Zhu and Y. Chai and W. Li and G. Ou},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.751438},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751438v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Spatially Confined Phase Separation Promotes Local Tubulin Availability to Stabilize Ciliary Microtubule Growth
AU  - K. XU
AU  - Z. Zhu
AU  - Y. Chai
AU  - W. Li
AU  - G. Ou
PY  - 2026
DA  - 2026/09/14
PB  - bioRxiv
DO  - 10.64898/2026.09.14.751438
UR  - https://www.biorxiv.org/content/10.64898/2026.09.14.751438v1
AB  - 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.
ER  -