The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein

Żyłkiewicz, Eliza; Kijańska, Monika; Choi, Won-Chan; Derewenda, Urszula; Derewenda, Zygmunt S.; Stukenberg, P. Todd

doi:10.1083/jcb.201011142

Cited by 80 publications

(138 citation statements)

References 41 publications

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“…NDEL1 (S251A), a single site mutant deficient in its susceptibility to Aurora-A pulled down almost no dynein (Zylkiewicz et al, 2011). Presumably, the C terminus of NDEL1 provides a regulatory mechanism for dynein binding, so that the unphosphorylated protein is autoinhibited (Zylkiewicz et al, 2011). Reductions of emanation frequency and emanation speed were rescued by expression of GFP-Ndel1 (S251E), but not by GFP-Ndel1 (S251A).…”

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 77%

“…Rather, CDK5 phosphorylation augments interaction with dynein (Hebbar et al, 2008). However, Zylkiewicz et al (2011) reported that double-mutant NDEL1 lacking two sites phosphorylated by CDK1 and CDK5 pulled down almost no dynein. This discrepancy may be attributable to the difference of experimental design.…”

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

“…However, we previously reported that the N terminus of NDEL1 restored LIS1-dependent suppression of dynein motility (Yamada et al, 2008;Torisawa et al, 2011), whereas the C terminus of NDEL1 had no effect on LIS1 suppression (Torisawa et al, 2011). In addition, Zylkiewicz et al (2011) reported that the N terminus of NDEL1 lacking the dynein-binding site (Sasaki et al, 2000) was fully able to rescue aster formation (Zylkiewicz et al, 2011). One plausible explanation is that phosphorylation at S251 of NDEL1 regulates the interaction with dynein or LIS1.…”

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

“…One plausible explanation is that phosphorylation at S251 of NDEL1 regulates the interaction with dynein or LIS1. NDEL1 (S251A), a single site mutant deficient in its susceptibility to Aurora-A pulled down almost no dynein (Zylkiewicz et al, 2011). Presumably, the C terminus of NDEL1 provides a regulatory mechanism for dynein binding, so that the unphosphorylated protein is autoinhibited (Zylkiewicz et al, 2011).…”

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

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Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

et al. 2012

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Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an “inside-out” gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A–NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition,in uteroinjection of the Aurora-A kinase-dead mutant provoked defective migration of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration. We found that CDK5RAP2 is a key molecule that mediates functional interaction and is essential for centrosomal targeting of Aurora-A. Our observations demonstrated novel and surprising cross talk between Aurora-A and CDK5 during neuronal migration.

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Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 77%

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

Section: Novel Role Of Mitotic Kinase In Neuronal Migrationmentioning

confidence: 99%

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Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

et al. 2012

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“…Both proteins can complex with cytoplasmic dynein, the retrograde microtubule motor. Lis1 and Ndel1 are proposed to be important for the regulation of dynein-related events in mitosis and migration (Shu et al, 2004, Yamada et al, 2008, Youn et al, 2009, Hippenmeyer et al, 2010, Zyłkiewicz et al, 2011. Thus, PSCs can provide an important model to study migration defects related to MAPs.…”

Section: Lis1 and Ndel1mentioning

confidence: 99%

Pluripotent Stem Cells as an In Vitro Model of Neuronal Differentiation

Kerkis¹,

Hayashi²,

Lizier³

et al. 2011

Embryonic Stem Cells - Differentiation and Pluripotent Alternatives

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Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Fourel

Boscheron

2020

FEBS Letters

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Malformations of cortical development (MCDs) are a group of severe brain malformations associated with intellectual disability and refractory childhood epilepsy. Human missense heterozygous mutations in the 9 α‐tubulin and 10 β‐tubulin isoforms forming the heterodimers that assemble into microtubules (MTs) were found to cause MCDs. However, how a single mutated residue in a given tubulin isoform can perturb the entire microtubule population in a neuronal cell remains a crucial question. Here, we examined 85 MCD‐associated tubulin mutations occurring in TUBA1A, TUBB2, and TUBB3 and their location in a three‐dimensional (3D) microtubule cylinder. Mutations hitting residues exposed on the outer microtubule surface are likely to alter microtubule association with partners, while alteration of intradimer contacts may impair dimer stability and straightness. Other types of mutations are predicted to alter interdimer and lateral contacts, which are responsible for microtubule cohesion, rigidity, and dynamics. MCD‐associated tubulin mutations surprisingly fall into all categories, thus providing unexpected insights into how a single mutation may impair microtubule function and elicit dominant effects in neurons.

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The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein

Abstract: Binding of the N terminus of Ndel1 to dynein facilitates microtubule self-organization in Ran-induced asters.

Cited by 80 publications

References 41 publications

Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

Pluripotent Stem Cells as an In Vitro Model of Neuronal Differentiation

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

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