A Selective Activity-Dependent Requirement for Dynamin 1 in Synaptic Vesicle Endocytosis

Author:

Ferguson Shawn M.12345,Brasnjo Gabor12345,Hayashi Mitsuko12345,Wölfel Markus12345,Collesi Chiara12345,Giovedi Silvia12345,Raimondi Andrea12345,Gong Liang-Wei12345,Ariel Pablo12345,Paradise Summer12345,O'Toole Eileen12345,Flavell Richard12345,Cremona Ottavio12345,Miesenböck Gero12345,Ryan Timothy A.12345,De Camilli Pietro12345

Affiliation:

1. Howard Hughes Medical Institute, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.

2. Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, USA.

3. Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.

4. Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

5. Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.

Abstract

Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity, branched, tubular plasma membrane invaginations accumulated, capped by clathrin-coated pits, in synapses of dynamin 1–knockout mice. Synaptic vesicle endocytosis was severely impaired during strong exogenous stimulation but resumed efficiently when the stimulus was terminated. Thus, dynamin 1–independent mechanisms can support limited synaptic vesicle endocytosis, but dynamin 1 is needed during high levels of neuronal activity.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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