Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons.

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Title: Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons.
Authors: Perlson, Eran1,2, Hendricks, Adam G.3, Lazarus, Jacob E.3, Ben-Yaakov, Keren1,2, Gradus, Tal1,2, Mariko Tokito3, Holzbaur, Erika L. F.3 holzbaur@mail.med.upenn.edu
Source: Journal of Biological Chemistry. 9/27/2013, Vol. 288 Issue 39, p27812-27824. 13p.
Subjects: Dynein, Neural cell adhesion molecule, Cell adhesion molecules, Microtubules, Neurons
Abstract: Cytoplasmic dynein is well characterized as an organelle motor, but dynein also acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we identify a novel and direct interaction between dynein and the 180-kDa isoform of the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate that dynein bound to beads via the NCAM180 interaction domain can tether projecting microtubule plus-ends. Live cell assays indicate that the NCAM180-dependent recruitment of dynein to the cortex leads to the selective stabilization of microtubules projecting to NCAM180 patches at the cell periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain extract and from synaptosomal fractions, consistent with an endogenous interaction in neurons. Thus, we examined microtubule dynamics and synaptic density in primary cortical neurons. We find that depletion of NCAM, inhibition of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low dose nocodazole all result in significantly decreased in synaptic density. Based on these observations, we propose a working model for the role of dynein at the synapse, in which the anchoring of the motor to the cortex via binding to an adhesion molecule mediates the tethering of dynamic microtubule plus-ends to potentiate synaptic stabilization. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons.
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  Data: <searchLink fieldCode="AR" term="%22Perlson%2C+Eran%22">Perlson, Eran</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Hendricks%2C+Adam+G%2E%22">Hendricks, Adam G.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Lazarus%2C+Jacob+E%2E%22">Lazarus, Jacob E.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ben-Yaakov%2C+Keren%22">Ben-Yaakov, Keren</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Gradus%2C+Tal%22">Gradus, Tal</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Mariko+Tokito%22">Mariko Tokito</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Holzbaur%2C+Erika+L%2E+F%2E%22">Holzbaur, Erika L. F.</searchLink><relatesTo>3</relatesTo><i> holzbaur@mail.med.upenn.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 9/27/2013, Vol. 288 Issue 39, p27812-27824. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Dynein%22">Dynein</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+cell+adhesion+molecule%22">Neural cell adhesion molecule</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+adhesion+molecules%22">Cell adhesion molecules</searchLink><br /><searchLink fieldCode="DE" term="%22Microtubules%22">Microtubules</searchLink><br /><searchLink fieldCode="DE" term="%22Neurons%22">Neurons</searchLink>
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  Data: Cytoplasmic dynein is well characterized as an organelle motor, but dynein also acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we identify a novel and direct interaction between dynein and the 180-kDa isoform of the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate that dynein bound to beads via the NCAM180 interaction domain can tether projecting microtubule plus-ends. Live cell assays indicate that the NCAM180-dependent recruitment of dynein to the cortex leads to the selective stabilization of microtubules projecting to NCAM180 patches at the cell periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain extract and from synaptosomal fractions, consistent with an endogenous interaction in neurons. Thus, we examined microtubule dynamics and synaptic density in primary cortical neurons. We find that depletion of NCAM, inhibition of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low dose nocodazole all result in significantly decreased in synaptic density. Based on these observations, we propose a working model for the role of dynein at the synapse, in which the anchoring of the motor to the cortex via binding to an adhesion molecule mediates the tethering of dynamic microtubule plus-ends to potentiate synaptic stabilization. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1074/jbc.M113.465088
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        Text: English
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        StartPage: 27812
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      – SubjectFull: Dynein
        Type: general
      – SubjectFull: Neural cell adhesion molecule
        Type: general
      – SubjectFull: Cell adhesion molecules
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      – SubjectFull: Microtubules
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      – TitleFull: Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons.
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              Text: 9/27/2013
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              Y: 2013
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