Native kinesin‐1 does not bind preferentially to GTP‐tubulin‐rich microtubules in vitro

Li, Qiaochu; King, Stephen J.; Xu, Jing

doi:10.1002/cm.21386

Cited by 9 publications

(8 citation statements)

References 67 publications

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“…In contrast, the neuron-specific kinesin motor KIF5C bound equally well to both microtubule types, as did KIF5B, a ubiquitously expressed isoform of the same kinesin-1 family ( Figures 4A and 4B). Although this observation contrasts with a previous report [35], it is supported by recent work using native KIF5 [36].…”

Section: Binding Of Kif1a To the Microtubule Lattice Is Negatively Mocontrasting

confidence: 99%

Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo Delivery to the Presynapse

et al. 2019

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Graphical Abstract Highlights d Delivery of synaptic vesicle precursors occurs with high precision d Presynaptic sites are hotspots of dynamic GTP-rich microtubule plus ends d KIF1A binds more weakly to the GTP lattice, rapidly detaching from plus ends d A human KIF1A mutation perturbs lattice sensing and reduces synaptic strength SUMMARYNeurons in the CNS establish thousands of en passant synapses along their axons. Robust neurotransmission depends on the replenishment of synaptic components in a spatially precise manner.Using live-cell microscopy and single-molecule reconstitution assays, we find that the delivery of synaptic vesicle precursors (SVPs) to en passant synapses in hippocampal neurons is specified by an interplay between the kinesin-3 KIF1A motor and presynaptic microtubules. Presynaptic sites are hotspots of dynamic microtubules rich in GTPtubulin. KIF1A binds more weakly to GTP-tubulin than GDP-tubulin and competes with end-binding (EB) proteins for binding to the microtubule plus end. A disease-causing mutation within KIF1A that reduces preferential binding to GDP-versus GTPrich microtubules disrupts SVP delivery and reduces presynaptic release upon neuronal stimulation. Thus, the localized enrichment of dynamic microtubules along the axon specifies a localized unloading zone that ensures the accurate delivery of SVPs, controlling presynaptic strength in hippocampal neurons.

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Section: Binding Of Kif1a To the Microtubule Lattice Is Negatively Mocontrasting

confidence: 99%

Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo Delivery to the Presynapse

et al. 2019

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“…We hypothesize that this faster stepping process can occur as the kinesin motor no longer has to pull the tubulin dimer in an elongated conformation 25 . While most studies using in vitro polymerized microtubules agree with our findings in neuronal cultures, some studies concerning kinesin-1 binding affinity and velocity report no significant difference between microtubules consisting of the elongated -or compacted tubulin conformation 56,57 . It should be noted that the latter studies compared similar conformational states of the tubulin dimer, i.e.…”

Section: Discussionsupporting

confidence: 87%

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

Steenbergen

Lavoie-Cardinal

Kazwiny³

et al. 2020

Preprint

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Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium.Mitochondrial transport requires and depends on microtubules which fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin both in vitro and in vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers, similar to GTP-tubulin, that are more straight and rigid. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin step processivity on microtubules consisting of elongated dimers underlies increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin controls mitochondrial motility and as such locally regulates the distribution of mitochondria along axons.

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“…Said binding depends on electrostatic interactions between kinesin and tubulin (Woehlke et al, 1997 ), and the interaction between motor and MTs seems to be stronger for kinesin 3 compared to kinesin-1 (Okada and Hirokawa, 2000 ; Atherton et al, 2014 ; Soppina and Verhey, 2014 ; Lessard et al, 2019 ). The nucleotide state of MTs can also influence the binding of kinesin-3, which displays higher affinity for GTP-like MTs (Guedes-Dias et al, 2019 ), while kinesin-1 preferences are still unclear (Nakata et al, 2011 ; Li et al, 2017 ; Guedes-Dias et al, 2019 ). A well-known example of MAPs, which has been reported to inhibit the binding and motility of kinesin-1 is Tau (Dixit et al, 2008 ; Kellogg et al, 2018 ; Monroy et al, 2018 ).…”

Section: Molecular Drivers Of Anterograde Axonal Transport and Their mentioning

confidence: 99%

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

Guillaud

El-Agamy

Otsuki

et al. 2020

Front. Mol. Neurosci.

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Neurons are highly polarized cells with an elongated axon that extends far away from the cell body. To maintain their homeostasis, neurons rely extensively on axonal transport of membranous organelles and other molecular complexes. Axonal transport allows for spatio-temporal activation and modulation of numerous molecular cascades, thus playing a central role in the establishment of neuronal polarity, axonal growth and stabilization, and synapses formation. Anterograde and retrograde axonal transport are supported by various molecular motors, such as kinesins and dynein, and a complex microtubule network. In this review article, we will primarily discuss the molecular mechanisms underlying anterograde axonal transport and its role in neuronal development and maturation, including the establishment of functional synaptic connections. We will then provide an overview of the molecular and cellular perturbations that affect axonal transport and are often associated with axonal degeneration. Lastly, we will relate our current understanding of the role of axonal trafficking concerning anterograde trafficking of mRNA and its involvement in the maintenance of the axonal compartment and disease.

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Native kinesin‐1 does not bind preferentially to GTP‐tubulin‐rich microtubules in vitro

Cited by 9 publications

References 67 publications

Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo Delivery to the Presynapse

Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo Delivery to the Presynapse

Nano-positioning and tubuline conformation determine transport of mitochondria along microtubules

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

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