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bioRxiv · 10.64898/2026.11.11.765876

Multivalent BBSome-IFT proximities support IFT-A-IFT-B coordination in vivo

Shen, Z.·Chen, G.·Li, M.·Chai, Y.·Li, W.·Ou, G.
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Abstract

Intraflagellar transport (IFT) depends on coordinated movement of IFT-A and IFT-B, yet how these assemblies remain coupled within dynamic ciliary trains is unclear. Here, we combine endogenous fluorescent knock-in tagging, quantitative in vivo FLIM-FRET, structural modeling, and targeted mutagenesis to define IFT organization in C. elegans and mammalian cells. FLIM-FRET mapping identifies proximity networks within IFT-B and places IFT144 near IFT172 and IFT88 in intact cilia. Loss of BBSome function is associated with weaker IFT-A-IFT-B proximity signals and divergent subcomplex transport dynamics, consistent with a contribution of the BBSome to IFT coordination in vivo. Split-GFP complementation places BBSome components near IFT-A and IFT-B, while structural modeling nominates complementary charged surfaces on the IFT46-IFT52 dimer and BBS7/BBS9. Charge-reversal mutations targeting these surfaces impair BBSome recruitment and functional rescue. Together, these findings support a model in which multivalent BBSome-IFT proximities contribute to IFT-A-IFT-B coordination during ciliary transport.

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Shen, Z., Chen, G., Li, M., Chai, Y., Li, W., Ou, G.. 2026-11-13. Multivalent BBSome-IFT proximities support IFT-A-IFT-B coordination in vivo. https://doi.org/10.64898/2026.11.11.765876

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