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Cdk5 is essential for synaptic vesicle endocytosis.
Timothy C Tan1, Valentina A Valova, Chandra S Malladi
1Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
Nature Cell Biology
|July 12, 2003
Summary
Cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I, maintaining synaptic vesicle endocytosis (SVE). This study identifies Cdk5 as the first dephosphin kinase crucial for SVE in nerve terminals.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Synaptic vesicle endocytosis (SVE) is essential for neurotransmission.
- SVE is regulated by the phosphorylation status of dephosphin proteins.
- The protein kinases responsible for rephosphorylating dephosphins in SVE have remained unidentified.
Purpose of the Study:
- To identify the protein kinase responsible for rephosphorylating dephosphins during synaptic vesicle endocytosis.
- To investigate the role of cyclin-dependent kinase 5 (Cdk5) in SVE.
Main Methods:
- In vitro phosphorylation assays using Cdk5 and dynamin I.
- In vivo studies using Cdk5 antagonists and dominant-negative Cdk5 expression in nerve terminals.
- Analysis of dynamin I, amphiphysin, and AP180 phosphorylation sites.
Main Results:
- Cdk5 directly phosphorylates dynamin I at Ser 774 and Ser 778 in vitro and in vivo.
- Inhibition of Cdk5 activity blocks dynamin I phosphorylation and impairs SVE.
- Cdk5 specifically phosphorylates dynamin I, not amphiphysin or AP180.
Conclusions:
- Cdk5 is the first identified dephosphin kinase involved in synaptic vesicle endocytosis.
- Cdk5 plays an essential role in maintaining SVE by phosphorylating dynamin I.
- These findings elucidate a key regulatory mechanism in synaptic vesicle recycling.