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

• Published in: Nature cell biology Vol. 25; no. 1; pp. 68 - 78
• Main Authors: Maan, Renu, Reese, Louis, Volkov, Vladimir A., King, Matthew R., van der Sluis, Eli O., Andrea, Nemo, Evers, Wiel H., Jakobi, Arjen J., Dogterom, Marileen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2023; Nature Publishing Group
• Subjects: 631/535/1258/1260; 631/80/128/1653; Accumulation; Biomedical and Life Sciences; Cancer Research; Cargo; Cell Biology; Cometary composition; Developmental Biology; Droplets; Dyneins - metabolism; Kinesin; Kinesins - genetics; Kinesins - metabolism; Life Sciences; Liquid phases; Microtubule-associated proteins; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Motor activity; Myosins - metabolism; Phase separation; Proteins; Schizosaccharomyces - genetics; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Stem Cells; Yeasts
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/s41556-022-01037-0

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.
Maan et al., Meier et al. and Song et al. report that microtubule plus-tip end binding proteins can undergo liquid–liquid phase separation and regulate microtubule dynamics.