A novel assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations

Bentley, Marvin; Decker, Helena; Luisi, Julie; Banker, Gary

doi:10.1083/jcb.201408056

Cited by 76 publications

(113 citation statements)

References 43 publications

(61 reference statements)

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“…4). A recent study has shown that the recruitment of the kinesin-3 proteins KIF1A and KIF1Bβ is also dependent on BORC and Arl8 (Guardia et al, 2016), as well as several parts of the C-terminal tail domain (Bentley et al, 2015;Guardia et al, 2016). Considerably less is known about the mechanisms that couple other kinesins to lysosomes.…”

Section: Anterograde Transportmentioning

confidence: 99%

“…Remarkably, lysosome movement has been shown to depend on not one but multiple kinesins, including kinesin-1 (KIF5A, KIF5B and KIF5C) (Nakata and Hirokawa, 1995;Tanaka et al, 1998;Rosa-Ferreira and Munro, 2011), kinesin-2 (KIF3) (Brown et al, 2005;Loubéry et al, 2008) and kinesin-3 (KIF1A and KIF1B) (Matsushita et al, 2004;Korolchuk et al, 2011;Bentley et al, 2015), as well as the kinesin-13 (KIF2) family members (Santama et al, 1998;Korolchuk et al, 2011) (Fig. 3).…”

Section: Anterograde Transportmentioning

confidence: 99%

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Mechanisms and functions of lysosome positioning

Guardia

Keren-Kaplan

et al. 2016

Journal of Cell Science

372

466

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Lysosomes have been classically considered terminal degradative organelles, but in recent years they have been found to participate in many other cellular processes, including killing of intracellular pathogens, antigen presentation, plasma membrane repair, cell adhesion and migration, tumor invasion and metastasis, apoptotic cell death, metabolic signaling and gene regulation. In addition, lysosome dysfunction has been shown to underlie not only rare lysosome storage disorders but also more common diseases, such as cancer and neurodegeneration. The involvement of lysosomes in most of these processes is now known to depend on the ability of lysosomes to move throughout the cytoplasm. Here, we review recent findings on the mechanisms that mediate the motility and positioning of lysosomes, and the importance of lysosome dynamics for cell physiology and pathology.

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Section: Anterograde Transportmentioning

confidence: 99%

Section: Anterograde Transportmentioning

confidence: 99%

Mechanisms and functions of lysosome positioning

Guardia

Keren-Kaplan

et al. 2016

Journal of Cell Science

372

466

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“…The strong accumulation that occurs at neurite tips in this assay likely reflects the high efficiency of kinesin translocation in neurons and the dense packing of microtubules in axons and dendrites. When kinesin motor domains are expressed in fibroblasts, small spots of fluorescence can be detected near the cell periphery (presumably sites where plus-ends are concentrated), but the majority of the fluorescence is evenly distributed throughout the cell (Bentley, Decker, Luisi, & Banker, 2015). …”

Section: Introductionmentioning

confidence: 99%

Analyzing kinesin motor domain translocation in cultured hippocampal neurons

Yang¹,

Bentley²,

Huang³

et al. 2016

Methods in Cell Biology

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Neuronal microtubules are subject to extensive posttranslational modifications and are bound by MAPs, tip-binding proteins, and other accessory proteins. All of these features, which are difficult to replicate in vitro, are likely to influence the translocation of kinesin motors. Here we describe assays for evaluating the translocation of a population of fluorescently labeled kinesin motor domains, based on their accumulation in regions of the cell enriched in microtubule plus ends. Neurons lend themselves to these experiments because of their microtubule organization. In axons, microtubules are oriented with their plus ends out; dendrites contain a mixed population of microtubules, but those near the tips are also plus end out. The assays involve the expression of constitutively active kinesins that can walk processively, but that lack the autoinhibitory domain in the tail that normally prevents their binding to microtubules until they attach to vesicles. The degree to which such motor domains accumulate at neurite tips serves as a measure of the efficiency of their translocation. Although these assays cannot provide the kind of quantitative kinetic information obtained from in vitro assays, they offer a simple way to examine kinesin translocation in living neurons. They can be used to compare the translocation efficiency of different kinesin motors and to evaluate how mutations or posttranslational modifications within the motor domain influence kinesin translocation. Changes to motor domain accumulation in these assays can also serve as readout for changes in the microtubule cytoskeleton that affect kinesin translocation.

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“…In fact, many of the ∼45 mammalian kinesins exclusively mediate axonal transport, and only a handful, including the kinesin-3 proteins KIF1A, KIF1Bβ, KIF1C, and KIF16B and the kinesin-4 proteins KIF21A and KIF21B, mediate organelle transport to axons and dendrites (24,25,67). Of these, KIF1A and KIF1Bβ have been reported to move late endosomes and lysosomes in nonneuronal cells (54,68,69). It would thus be of interest to test if KIF1A and KIF1Bβ mediate lysosome transport in dendrites.…”

Section: Requirement Of Borc-dependent Lysosome Transport For Autophamentioning

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.

175

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 assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations

Abstract: A novel assay based on expressing FRB-tagged candidate vesicle-binding protein reveals that KIF13A and KIF13B bind preferentially to early endosomes, whereas KIF1A and KIF1Bβ bind preferentially to late endosomes and lysosomes.

Cited by 76 publications

References 43 publications

Mechanisms and functions of lysosome positioning

Mechanisms and functions of lysosome positioning

Analyzing kinesin motor domain translocation in cultured hippocampal neurons

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

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