1. MAP7 family proteins regulate kinesin-1 recruitment and activation
- Author
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Hooikaas, Peter Jan, Martin, Maud, Mühlethaler, Tobias, Kuijntjes, Gert Jan, Peeters, Cathelijn A.E., Katrukha, Eugene A., Ferrari, Luca, Stucchi, Riccardo, Verhagen, Daan G.F., Van Riel, Wilhelmina E., Grigoriev, Ilya, Altelaar, A. F.Maarten, Hoogenraad, Casper C., Rüdiger, Stefan G.D., Steinmetz, Michel O., Kapitein, Lukas C., Akhmanova, Anna, Sub Cell Biology, Sub Cellular Protein Chemistry, Afd Biomol.Mass Spect. and Proteomics, Celbiologie, Biomolecular Mass Spectrometry and Proteomics, Cellular Protein Chemistry, Sub Cell Biology, Sub Cellular Protein Chemistry, Afd Biomol.Mass Spect. and Proteomics, Celbiologie, Biomolecular Mass Spectrometry and Proteomics, and Cellular Protein Chemistry
- Subjects
Allosteric effect ,Kinesins ,Diketopiperazines ,macromolecular substances ,Microtubules ,Article ,HeLa ,03 medical and health sciences ,0302 clinical medicine ,Microtubule ,Chlorocebus aethiops ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Research Articles ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Processivity ,Cell Biology ,biology.organism_classification ,In vitro ,Mitochondria ,3. Good health ,Cell biology ,Enzyme Activation ,Protein Transport ,Lower affinity ,HEK293 Cells ,Benzamides ,COS Cells ,Kinesin ,Microtubule-Associated Proteins ,Linker ,030217 neurology & neurosurgery ,HeLa Cells ,Protein Binding - Abstract
Hooikaas et al. show that mammalian MAP7 family proteins act redundantly to activate the kinesin-1 motor protein. Using experiments in cells and in vitro reconstitution assays, they demonstrate that MAP7 proteins promote microtubule recruitment and processivity of kinesin-1 by transiently associating with the stalk region of the motor., 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.
- Published
- 2019