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Document Type |
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Article In Journal |
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Document Title |
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Mechanism of Activity-Dependent Cargo Loading via the Phosphorylation of KIF3A by PKA and CaMKIIa. Mechanism of Activity-Dependent Cargo Loading via the Phosphorylation of KIF3A by PKA and CaMKIIa. |
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Document Language |
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English |
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Abstract |
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A regulated mechanism of cargo loading is crucial for intracellular transport. N-cadherin, a synaptic adhesion molecule that is critical for neuronal function, must be precisely transported to dendritic spines in response to synaptic activity and plasticity. However, the mechanism of activity-dependent cargo loading remains unclear. To elucidate this mechanism, we investigated the activity-dependent transport of N-cadherin via its transporter, KIF3A. First, by comparing KIF3A-bound cargo vesicles with unbound KIF3A, we identified critical KIF3A phosphorylation sites and specific kinases, PKA and CaMKIIa, using quantitative phosphoanalyses. Next, mutagenesis and kinase inhibitor experiments revealed that N-cadherin transport was enhanced via phosphorylation of the KIF3A C terminus, thereby increasing cargo-loading activity. Furthermore, N-cadherin transport was enhanced during homeostatic upregulation of synaptic strength, triggered by chronic inactivation by TTX. We propose the first model of activity-dependent cargo loading, in which phosphorylation of the KIF3A C terminus upregulates the loading and transport of N-cadherin in homeostatic synaptic plasticity. |
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ISSN |
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0896-6273 |
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Journal Name |
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Neuron |
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Volume |
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87 |
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Issue Number |
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5 |
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Publishing Year |
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1436 AH
2015 AD |
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Article Type |
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Article |
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Added Date |
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Wednesday, April 20, 2016 |
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Researchers
| Sotaro Ichinose | Ichinose, Sotaro | Investigator | | |
| Tadayuki Ogawa | Ogawa, Tadayuki | Researcher | | |
| Nobutaka Hirokawa | Hirokawa, Nobutaka | Researcher | | hirokawa@m.u-tokyo.ac.jp |
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