Structure and mechanism of microtubule stabilization and motor regulation by MAP9
Cetin, B.; Taheri, A.; Golcuk, M.; Monroy, B. Y.; Fernandes, J.; Ori-McKenney, K. M.; Gur, M.; Nogales, E.; Yildiz, A.
Show abstract
Microtubule-associated proteins (MAPs) regulate the organization of microtubules and control intracellular transport, but their individual contributions to microtubule dynamics and motor regulation remain poorly understood. Here, we identify MAP9 as a critical factor that stabilizes microtubules and facilitates neuronal morphogenesis. MAP9 knockdown abolishes the outgrowth of neurites, a phenotype not observed through the loss of other neuronal MAPs. Cryo-electron microscopy revealed that, unlike other MAPs that bind along protofilaments, MAP9 binds around the microtubule as a long alpha helix using five consecutive repeats. This unique binding mode enables MAP9 to staple adjacent protofilaments, thereby preventing microtubule depolymerization. We also showed that MAP9 selectively permits kinesin-3 motility while hindering kinesin-1 through interactions with a divergent loop-8 of their motor domains. Our results establish MAP9 as a key MAP required for neuronal growth and uncover how it differentially regulates intracellular transport driven by kinesin motors.
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