Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.
Clayton, Emma L
Smillie, Karen J
Cole, Adam R
Wyllie, David J
Robinson, Phillip J
Cousin, Michael A
Springer Science and Business Media LLC
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Clayton, E. L., Sue, N., Smillie, K. J., O'Leary, T., Bache, N., Cheung, G., Cole, A. R., et al. (2010). Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.. Nat Neurosci, 13 (7), 845-851. https://doi.org/10.1038/nn.2571
Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity.
Cerebellum, Hippocampus, Neurons, Presynaptic Terminals, Synaptic Vesicles, Cells, Cultured, Animals, Rats, Rats, Sprague-Dawley, Dynamin I, Glycogen Synthase Kinase 3, Signal Transduction, Endocytosis, Phosphorylation, Male, Cyclin-Dependent Kinase 5, In Vitro Techniques
Wellcome Trust (080066/Z/06/Z)
External DOI: https://doi.org/10.1038/nn.2571
This record's URL: https://www.repository.cam.ac.uk/handle/1810/308025
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