MAP7 family proteins regulate kinesin-1 recruitment and activation.

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1-dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules. © 2019 Hooikaas et al.

Citation

Peter Jan Hooikaas, Maud Martin, Tobias Mühlethaler, Gert-Jan Kuijntjes, Cathelijn A E Peeters, Eugene A Katrukha, Luca Ferrari, Riccardo Stucchi, Daan G F Verhagen, Wilhelmina E van Riel, Ilya Grigoriev, A F Maarten Altelaar, Casper C Hoogenraad, Stefan G D Rüdiger, Michel O Steinmetz, Lukas C Kapitein, Anna Akhmanova. MAP7 family proteins regulate kinesin-1 recruitment and activation. The Journal of cell biology. 2019 Apr 01;218(4):1298-1318

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PMID: 30770434

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