14-3-3 regulation of Ncd reveals a new mechanism for targeting proteins to the spindle in oocytes

Beaven, Robin; Bastos, Ricardo; Spanos, Christos; Romé, Pierre; Cullen, C. Fiona; Rappsilber, Juri; Giet, Régis; Goshima, Gohta; Ohkura, Hiroyuki

doi:10.1083/jcb.201704120

Cited by 29 publications

(65 citation statements)

References 48 publications

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“…Such events may be under the control of environmental factors that elicit signaling cascades relevant to KIFC1. KIFC1 can be degraded by a CDK1-dependent event (Singh et al, 2014) or another phosphorylation pathway (Molodtsov et al, 2016;Beaven et al, 2017), either of which could thrust a motile growth cone into a period of stalling or an axon into a bout of retraction. Dendrites might use KIFC1 quite differently from axons given that dendrites contain microtubules of mixed polarity orientation (Baas et al, 1991;Sharp et al, 1995;Lin et al, 2012;Yau et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon

Muralidharan

Baas

2019

J. Neurosci.

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KIFC1 (also called HSET or kinesin-14a) is best known as a multifunctional motor protein essential for mitosis. The present studies are the first to explore KIFC1 in terminally postmitotic neurons. Using RNA interference to partially deplete KIFC1 from rat neurons (from animals of either gender) in culture, pharmacologic agents that inhibit KIFC1, and expression of mutant KIFC1 constructs, we demonstrate critical roles for KIFC1 in regulating axonal growth and retraction as well as growth cone morphology. Experimental manipulations of KIFC1 elicit morphological changes in the axon as well as changes in the organization, distribution, and polarity orientation of its microtubules. Together, the results indicate a mechanism by which KIFC1 binds to microtubules in the axon and slides them into alignment in an ATP-dependent fashion and then cross-links them in an ATP-independent fashion to oppose their subsequent sliding by other motors.Here, we establish that KIFC1, a molecular motor well characterized in mitosis, is robustly expressed in neurons, where it has profound influence on the organization of microtubules in a number of different functional contexts. KIFC1 may help answer long-standing questions in cellular neuroscience such as, mechanistically, how growth cones stall and how axonal microtubules resist forces that would otherwise cause the axon to retract. Knowledge about KIFC1 may help researchers to devise strategies for treating disorders of the nervous system involving axonal retraction given that KIFC1 is expressed in adult neurons as well as developing neurons.

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Section: Discussionmentioning

confidence: 99%

Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon

Muralidharan

Baas

2019

J. Neurosci.

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“…We and others have suggested that restricting spindle assembly proximal to the chromosomes involves inhibition of spindle assembly factors in the cytoplasm (Beaven et al, 2017;Das et al, 2018;Rome and Ohkura, 2018). For example, the kinesin NCD that has been shown to be inhibited by 14-3-3, which is released by Aurora B phosphorylation (Beaven et al, 2017). We propose that the release of the CPC from the chromosomes locally overrides this inhibition and activates spindle assembly factors.…”

Section: Cpc-dependent Chromosome-directed Spindle Assembly In Oocytmentioning

confidence: 76%

“…Third, and most important, it explains how spindle assembly is restricted to the chromosomes in an acentrosomal system (Ohkura, 2015;Reschen et al, 2012;Rome and Ohkura, 2018); it is based on an HP1-Borealin interaction. We and others have suggested that restricting spindle assembly proximal to the chromosomes involves inhibition of spindle assembly factors in the cytoplasm (Beaven et al, 2017;Das et al, 2018;Rome and Ohkura, 2018). For example, the kinesin NCD that has been shown to be inhibited by 14-3-3, which is released by Aurora B phosphorylation (Beaven et al, 2017).…”

Section: Cpc-dependent Chromosome-directed Spindle Assembly In Oocytmentioning

confidence: 99%

“…Spindle assembly likely involves suppressing microtubule depolymerases, such as kinesin 13/MCAK and Op18/Stathmin (Kelly et al, 2007;Sampath et al, 2004). Spindle assembly also involves activating spindle promoting factors such as kinetochore proteins (Emanuele et al, 2008;Haase et al, 2017) and kinesins that bundle microtubules (Beaven et al, 2017;Das et al, 2018).…”

Section: Cpc-dependent Chromosome-directed Spindle Assembly In Oocytmentioning

confidence: 99%

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Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

Wang

Defosse

Jang

et al. 2020

Preprint

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The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosomal passenger complex (CPC), which consists of INCENP, Borealin, Survivin and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and HP1 is crucial for the initial recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. We also found that HP1 moves from the chromosomes to the spindle microtubules along with the CPC, and based on this, propose a mechanism for how the CPC moves from the chromosomes to the microtubules. Within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.

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“…cDNAs were then recombined into Gateway destination vectors using LR Clonase II reaction following the manufacturer’s protocol (Invitrogen). To generate transgenic flies expressing a GFP-tagged protein under the UASp promoter, we used φPGW modified from destination vector pPGW of the Murphy’s Gateway collection (https://emb.carnegiescience.edu/drosophila-gateway-vector-collection) by adding the φC31 attB recombination site (Beaven et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

Romé

Ohkura

2018

Preprint

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1The meiotic spindle in oocytes is assembled in the absence of centrosomes, the major 2 microtubule nucleation sites in mitotic and male meiotic cells. A crucial, yet unresolved 3 question in meiosis is how spindle microtubules are generated without centrosomes and 4 only around chromosomes in the large volume of oocytes. Here we report a novel oocyte-5 specific microtubule nucleation pathway that is essential for assembling most spindle 6 microtubules complementarily with the Augmin pathway, and sufficient for triggering 7 microtubule assembly in oocytes. This pathway is mediated by the kinesin-6 Subito/MKlp2, 8 which recruits the γ-tubulin complex to the spindle equator to nucleate microtubules in 9 Drosophila oocytes. Away from chromosomes, Subito interaction with the γ-tubulin complex 10 is suppressed by its N-terminal region to prevent ectopic microtubule assembly in oocytes. 11We further demonstrate that the Subito complex from ovaries can nucleate microtubules 12 from pure tubulin dimers in vitro. Taken together, microtubule nucleation regulated by 13Subito drives spatially restricted spindle assembly in oocytes.14 15 not peer-reviewed)

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14-3-3 regulation of Ncd reveals a new mechanism for targeting proteins to the spindle in oocytes

Abstract: 14-3-3 interacts with the kinesin-14 Ncd and prevents it from binding microtubules. Aurora B provides a spatial cue that releases Ncd from 14-3-3 around chromosomes, allowing Ncd to selectively bind the spindle microtubules in the large volume of oocytes.

Cited by 29 publications

References 48 publications

Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon

Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon

Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

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