Document Type |
: |
Article In Journal |
Document Title |
: |
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. |
Document Language |
: |
English |
Abstract |
: |
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. |
ISSN |
: |
0896-6273 |
Journal Name |
: |
Neuron |
Volume |
: |
87 |
Issue Number |
: |
5 |
Publishing Year |
: |
1436 AH
2015 AD |
Article Type |
: |
Article |
Added Date |
: |
Wednesday, April 20, 2016 |
|
Researchers
Sotaro Ichinose | Ichinose, Sotaro | Investigator | | |
Tadayuki Ogawa | Ogawa, Tadayuki | Researcher | | |
Nobutaka Hirokawa | Hirokawa, Nobutaka | Researcher | | hirokawa@m.u-tokyo.ac.jp |
|