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Science 316 (5824): 570-574

Copyright © 2007 by the American Association for the Advancement of Science

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

Shawn M. Ferguson,1,2,3 Gabor Brasnjo,5* Mitsuko Hayashi,1,2,3* Markus Wölfel,3 Chiara Collesi,1,2,3,7 Silvia Giovedi,1,2,3 Andrea Raimondi,1,2,3 Liang-Wei Gong,1,2,3 Pablo Ariel,5,6 Summer Paradise,1,2,3 Eileen O'Toole,8 Richard Flavell,1,4 Ottavio Cremona,7 Gero Miesenböck,3 Timothy A. Ryan,5 Pietro De Camilli1,2,3{dagger}

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.

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.
6 David Rockefeller Graduate Program, The Rockefeller University, New York, NY 10021, USA.
7 IFOM, the FIRC Institute for Molecular Oncology Foundation, and Università Vita—Salute San Raffaele, Milano, Italy.
8 Boulder Laboratory for 3D Electron Microscopy of Cells, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

* These authors contributed equally.

{dagger} To whom correspondence should be addressed. E-mail: pietro.decamilli{at}

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