par Hooikaas, Peter Jan;Martin, Maud ;Mühlethaler, Tobias;Kuijntjes, Gert-Jan;Peeters, Cathelijn A E;Katrukha, Eugene A;Ferrari, Luca;Stucchi, Riccardo;Verhagen, Daan DGF;van Riel, Wilhelmina W.E.;Grigoriev, Ilya;Altelaar, Maarten AFM;Hoogenraad, Casper CC;Rüdiger, Stefan G D;Steinmetz, Michel MO;Kapitein, Lukas C;Akhmanova, Anna
Référence The Journal of cell biology, 218, 4, page (1298-1318)
Publication Publié, 2019-05-01
Référence The Journal of cell biology, 218, 4, page (1298-1318)
Publication Publié, 2019-05-01
Article révisé par les pairs
Résumé : | 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. |