Multivalent interactions facilitate motor-dependent protein accumulation at growing microtubule plus-ends.

Renu Maan, Louis Reese, Vladimir A Volkov, Matthew R King, Eli O van der Sluis, Nemo Andrea, Wiel H Evers, Arjen J Jakobi, Marileen Dogterom

Nature cell biology 2023 Jan

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Growing microtubule ends organize end-tracking proteins into comets of mixed composition. Here using a reconstituted fission yeast system consisting of end-binding protein Mal3, kinesin Tea2 and cargo Tip1, we found that these proteins can be driven into liquid-phase droplets both in solution and at microtubule ends under crowding conditions. In the absence of crowding agents, cryo-electron tomography revealed that motor-dependent comets consist of disordered networks where multivalent interactions may facilitate non-stoichiometric accumulation of cargo Tip1. We found that two disordered protein regions in Mal3 are required for the formation of droplets and motor-dependent accumulation of Tip1, while autonomous Mal3 comet formation requires only one of them. Using theoretical modelling, we explore possible mechanisms by which motor activity and multivalent interactions may lead to the observed enrichment of Tip1 at microtubule ends. We conclude that microtubule ends may act as platforms where multivalent interactions condense microtubule-associated proteins into large multi-protein complexes. © 2022. The Author(s).

Citation

Renu Maan, Louis Reese, Vladimir A Volkov, Matthew R King, Eli O van der Sluis, Nemo Andrea, Wiel H Evers, Arjen J Jakobi, Marileen Dogterom. Multivalent interactions facilitate motor-dependent protein accumulation at growing microtubule plus-ends. Nature cell biology. 2023 Jan;25(1):68-78