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. |
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| 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.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 90489226 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons. – Name: Author Label: Authors Group: Au 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> – Name: TitleSource Label: Source Group: Src 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. – Name: Subject Label: Subjects Group: Su 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> – Name: Abstract Label: Abstract Group: Ab 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: Group: Ab 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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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M113.465088 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 27812 Subjects: – SubjectFull: Dynein Type: general – SubjectFull: Neural cell adhesion molecule Type: general – SubjectFull: Cell adhesion molecules Type: general – SubjectFull: Microtubules Type: general – SubjectFull: Neurons Type: general Titles: – TitleFull: Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Perlson, Eran – PersonEntity: Name: NameFull: Hendricks, Adam G. – PersonEntity: Name: NameFull: Lazarus, Jacob E. – PersonEntity: Name: NameFull: Ben-Yaakov, Keren – PersonEntity: Name: NameFull: Gradus, Tal – PersonEntity: Name: NameFull: Mariko Tokito – PersonEntity: Name: NameFull: Holzbaur, Erika L. F. IsPartOfRelationships: – BibEntity: Dates: – D: 27 M: 09 Text: 9/27/2013 Type: published Y: 2013 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 288 – Type: issue Value: 39 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
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