Document Details

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

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Sotaro IchinoseIchinose, Sotaro Investigator  
Tadayuki OgawaOgawa, Tadayuki Researcher  
Nobutaka HirokawaHirokawa, Nobutaka Researcher hirokawa@m.u-tokyo.ac.jp

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