A novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations

Jenkins, Brian V.; Decker, Helena; Bentley, Marvin; Luisi, Julie; Banker, Gary

doi:10.1083/jcb.201205070

Cited by 70 publications

(105 citation statements)

References 45 publications

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“…These findings imply that vesicles carrying the somatodendritic proteins examined in this study (TfR and NiV-F) do not depend on kinesin-1 for transport to the dendrites. Instead, these vesicles might acquire other plus-end directed kinesins (Setou et al, 2000; Chu et al, 2006; Song et al, 2009; Jenkins et al, 2012; Huang and Banker, 2012) or the minus-end directed dynein (Zheng et al, 2008; Kapitein et al, 2010) for movement within the somatodendritic domain. The potential use of both plus-end and minus-end directed microtubule motors for somatodendritic transport is supported by the existence of mixed-polarity microtubules in the dendrites of hippocampal neurons (Baas et al, 1988; Burton, 1988).…”

Section: Discussionmentioning

confidence: 99%

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

et al. 2015

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Summary Polarized sorting of newly-synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves become sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS) is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock herein referred to as the “pre-axonal exclusion zone” (PAEZ). Forced coupling of a somatodendritic cargo protein to an axonally-directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.

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Section: Discussionmentioning

confidence: 99%

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

et al. 2015

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“…KIF21A is restricted to the axon, and KIF21B localizes to both axons and dendrites (Jenkins et al, 2012; Marszalek et al, 1999), making it one of only a few kinesins to exhibit significant dendritic localization (Huang and Banker, 2012; Setou et al, 2002). The recent characterization of the KIF21B knockout mouse highlights the importance of this kinesin, as KIF21B −/− neurons exhibit decreased dendritic branching and spine density, coupled with a reduction in surface expression of synaptic receptors (Muhia et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B

Ghiretti

Thies

Tokito

et al. 2016

Neuron

137

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Summary The dendritic arbor is subject to continual activity-dependent remodeling, requiring a balance between directed cargo trafficking and dynamic restructuring of the underlying microtubule tracks. How cytoskeletal components are able to dynamically regulate these processes to maintain this balance remains largely unknown. By combining single molecule assays and live imaging in rat hippocampal neurons, we have identified the kinesin-4 KIF21B as a molecular regulator of activity-dependent trafficking and microtubule dynamicity in dendrites. We find that KIF21B contributes to the retrograde trafficking of BDNF/TrkB complexes, and also regulates microtubule dynamics through a separable, non-motor microtubule-binding domain. Neuronal activity enhances the motility of KIF21B at the expense of its role in cytoskeletal remodeling, the first example of a kinesin whose function is directly tuned to neuronal activity state. These studies suggest a model in which KIF21B navigates the complex cytoskeletal environment of dendrites by compartmentalizing functions in an activity-dependent manner.

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“…These distinct properties determine the specificity and direction of organelle movement by different microtubule motors in different regions of the neuron. Of the ∼45 kinesins encoded in mammalian genomes, many mediate axonal anterograde transport, whereas a few additionally drive transport in the dendrites (23)(24)(25). In contrast, there is only one cytoplasmic dynein in mammals that mediates retrograde transport in the axon, as well as transport in the dendrites (26,27).…”

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confidence: 99%

BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

Farı́as

Guardia

Pace

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

179

234

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The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

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A novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations

Abstract: A novel split kinesin assay identifies three Kinesin-3 family members that specifically interact with dendritic vesicle populations in neurons.

Cited by 70 publications

References 45 publications

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B

BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

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