Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends

Abstract

Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.

Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers

“…We suggest that distinct kinesin family members differentially regulate axonal TrkB trafficking. Interestingly, a recent study dissected the collaborative roles of the kinesin-1 and kinesin-3 pair KIF5B and KIF13B in peripheral transport of secretory Rab6 carrier in HeLa cells ( Serra-Marques et al., 2020 ). A previous work from our lab described a mechanism for selective cargo axon entry in DRG neurons that is based on the coordinated action of the coordinated action of kinesin-1 and kinesin-3 motors at the pre-axonal filtering zone ( Gumy et al., 2017 ).…”

Actin and an unconventional myosin motor, TgMyoF, control the organization and dynamics of the endomembrane network in Toxoplasma gondii

“…Although the movement of Rab6 vesicles was actin dependent in T. gondii, in mammalian cells there is a coordination between the actin and microtubule cytoskeletons to control movement in the endo-lysosomal system [57] and in other eukaryotes Rab6 vesicles are associated with both kinesin and dynein motors [58][59][60]. Thus, we sought to determine if microtubules played a role in either Rab6 compartment dynamics or Rab6 vesicle transport (Fig 3G -3J).…”

Mammalian Neuronal mRNA Transport Complexes: The Few Knowns and the Many Unknowns

“…Results from knockdown or overexpression studies are often difficult to interpret, as it is challenging to disentangle phenotypes caused by the pleiotropic functions of proteins required for mRNA transport, such as RBPs and motor proteins. For instance, several RBPs involved in neuronal mRNA transport, such as Fragile X Mental Retardation Protein (FMRP) (Dictenberg et al, 2008 ; Goering et al, 2020 ), are also required for nuclear processes (Shah et al, 2020 ), nuclear mRNA export (Zhang et al, 2007 ; Edens et al, 2019 ), and translation regulation (Feng et al, 1997 ), whereas an mRNP-transporting motor protein like kinesin-1 KIF5 transports a variety of cargoes (Twelvetrees et al, 2010 ; Nakajima et al, 2012 ; Barry et al, 2014 ; Heisler et al, 2014 ; Ruane et al, 2016 ; Henrichs et al, 2020 ; Serra-Marques et al, 2020 ). Hence, analyzing the potential role of an RBP or a motor protein in mRNA transport using knockdowns or overexpressions will inevitably affect multiple cellular processes, making the interpretation of results difficult.…”