mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1

Yamada, Masami; Toba, Shiori; Takitoh, Takako; Yoshida, Yuko; Mori, Daisuke; Nakamura, Takeshi; Iwane, Atsuko H.; Yanagida, Toshio; Imai, Haruo; Yu-Lee, Li-Yuan; Schroer, Trina A.; Wynshaw‐Boris, Anthony; Hirotsune, Shinji

doi:10.1038/emboj.2009.378

Cited by 59 publications

(63 citation statements)

References 45 publications

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“…We previously demonstrated that LIS1 arrests dynein motility (Fig. 1a: lanes 1 and 2, Supplementary Movies 1 and 2) and that kinesin-1 transports a LIS1-dynein-tubulin complex to plus ends of MTs via mNUDC 9,10 . Before dynein can function as a retrograde motor, idling dynein must be activated to bind cargoes.…”

Section: Resultsmentioning

confidence: 99%

Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement

et al. 2013

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Cytoplasmic dynein drives the movement of a wide range of cargoes towards the minus ends of microtubules. We previously demonstrated that LIS1 forms an idling complex with dynein, which is transported to the plus ends of microtubules by kinesin motors. Here we report that the small GTPase Rab6a is essential for activation of idling dynein. Immunoprecipitation and microtubule pull-down assays reveal that the GTP bound mutant, Rab6a(Q72L), dissociates LIS1 from a LIS1-dynein complex, activating dynein movement in in vitro microtubule gliding assays. We monitor transient interaction between Rab6a(Q72L) and dynein in vivo using dual-colour fluorescence cross-correlation spectroscopy in dorsal root ganglion (DRG) neurons. Finally, we demonstrate that Rab6a(Q72L) mediates LIS1 release from a LIS1-dynein complex followed by dynein activation through an in vitro single-molecule assay using triplecolour quantum dots. Our findings reveal a surprising function for GTP bound Rab6a as an activator of idling dynein.

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Section: Resultsmentioning

confidence: 99%

Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement

et al. 2013

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“…Most recently, Yamada et al (2010) demonstrated that, in cultured neurons, kinesin-1 binds and transports "transportable microtubules" (tMTs) via mammalian nuclear distribution gene C homolog (mNUDC). These tMTs act as carriers to transport cytoplasmic dynein.…”

Section: Discussionmentioning

confidence: 99%

TheCaenorhabditis elegansJIP3 Protein UNC-16 Functions As an Adaptor to Link Kinesin-1 with Cytoplasmic Dynein

Arimoto¹,

Koushika²,

Choudhary³

et al. 2011

J. Neurosci.

114

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Kinesin-1 is a microtubule plus-end-directed motor that transports various cargos along the axon. Previous studies have elucidated the physical and genetic interactions between kinesin-1 and cytoplasmic dynein, a microtubule minus-end-directed motor, in neuronal cells. However, the physiological importance of kinesin-1 in the dynein-dependent retrograde transport of cargo molecules remains obscure. Here, we show that Caenorhabditis elegans kinesin-1 forms a complex with dynein via its interaction with UNC-16, which binds to the dynein light intermediate (DLI) chain. Both kinesin-1 and UNC-16 are required for localization of DLI-1 at the plus ends of nerve process microtubules. In addition, retrograde transport of APL-1 depends on kinesin-1, UNC-16, and dynein. These results suggest that kinesin-1 mediates the anterograde transport of dynein using UNC-16 as a scaffold and that dynein in turn mediates the retrograde transport of cargo molecules in vivo. Thus, UNC-16 functions as an adaptor for kinesin-1-mediated transport of dynein.

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“…nudA, nudF and nudE encode dynein HC, LIS1 and NDEL/ NDE1, respectively. Mammalian NUDC is required for kinesin-1-mediated anterograde transport of dynein 39 . Presumably, mutation of LC8 will lead to impairment not only of the unloading of cargoes but also dynein recycling.…”

Section: Discussionmentioning

confidence: 99%

Arl3 and LC8 regulate dissociation of dynactin from dynein

et al. 2014

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Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. However, the regulatory mechanism underlying release of dynactin bound cargoes from dynein motor remains largely unknown. Here we report that ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 induce dissociation of dynactin from dynein. Immunoprecipitation and microtubule pull-down assays revealed that Arl3(Q71L) and LC8 facilitated detachment of dynactin from dynein. We also demonstrated Arl3(Q71L) or LC8-mediated dynactin release from a dynein-dynactin complex through trace experiments using quantum dot (Qdot)-conjugated proteins. Furthermore, we disclosed interactions of Arl3 and LC8 with dynactin and dynein, respectively, by live-cell imaging. Finally, knockdown (KD) of Arl3 and LC8 by siRNA induced abnormal localizations of dynein, dynactin and related organelles. Our findings uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the unloading regulation of dynactin-bound cargo from dynein motor.

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mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1

Cited by 59 publications

References 45 publications

Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement

Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement

TheCaenorhabditis elegansJIP3 Protein UNC-16 Functions As an Adaptor to Link Kinesin-1 with Cytoplasmic Dynein

Arl3 and LC8 regulate dissociation of dynactin from dynein

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