Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments

0533424 - BTÚ 2021 RIV GB eng J - Článek v odborném periodiku
Henrichs, Verena - Gryčová, Lenka - Bařinka, Cyril - Nahácka, Zuzana - Neužil, Jiří - Diez, S. - Rohlena, Jakub - Braun, Marcus - Lánský, Zdeněk
Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments.
Nature Communications. Roč. 11, č. 1 (2020). E-ISSN 2041-1723
Grant CEP: GA MŠMT(CZ) LM2015043; GA ČR GA19-20553S; GA ČR(CZ) GA20-04068S; GA ČR(CZ) GA20-18513S; GA MŠMT(CZ) LM2018129; GA ČR(CZ) GA18-08304S; GA ČR(CZ) GA18-10832S; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:86652036
Klíčová slova: axonal-transport * heavy-chain * alzheimers-disease * in-vitro
Obor OECD: 1.7 Other natural sciences
Impakt faktor: 14.919, rok: 2020
Způsob publikování: Open access
https://www.nature.com/articles/s41467-020-16972-5.pdf

Intracellular trafficking of organelles, driven by kinesin-1 stepping along microtubules, underpins essential cellular processes. In absence of other proteins on the microtubule surface, kinesin-1 performs micron-long runs. Under crowding conditions, however, kinesin-1 motility is drastically impeded. It is thus unclear how kinesin-1 acts as an efficient transporter in intracellular environments. Here, we demonstrate that TRAK1 (Milton), an adaptor protein essential for mitochondrial trafficking, activates kinesin-1 and increases robustness of kinesin-1 stepping on crowded microtubule surfaces. Interaction with TRAK1 i) facilitates kinesin-1 navigation around obstacles, ii) increases the probability of kinesin-1 passing through cohesive islands of tau and iii) increases the run length of kinesin-1 in cell lysate. We explain the enhanced motility by the observed direct interaction of TRAK1 with microtubules, providing an additional anchor for the kinesin-1-TRAK1 complex. Furthermore, TRAK1 enables mitochondrial transport in vitro. We propose adaptor-mediated tethering as a mechanism regulating kinesin-1 motility in various cellular environments. Intracellular trafficking of organelles is driven by kinesin-1 stepping along microtubules, but crowding conditions impede kinesin-1 motility. Here authors demonstrate that TRAK1, an adaptor protein essential for mitochondrial trafficking, activates kinesin-1 and increases robustness of kinesin-1 stepping on crowded microtubule surfaces.
Trvalý link: http://hdl.handle.net/11104/0311819