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

doi:10.1126/science.1140621

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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

Abstract: Dynamin 1 is a neuron-specific guanosine triphosphatase thoughtto be critically required for the fission reaction of synapticvesicle endocytosis. Unexpectedly, mice lacking dynamin 1 wereable to form functional synapses, even though their postnatalviability was limited. However, during spontaneous network activity,branched, tubular plasma membrane invaginations accumulated,capped by clathrin-coated pits, in synapses of dynamin 1–knockoutmice. Synaptic vesicle endocytosis was severely impaired duringstrong exogenous stimulation but resumed efficiently when thestimulus was terminated. Thus, dynamin 1–independent mechanismscan support limited synaptic vesicle endocytosis, but dynamin1 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.

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

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