Turbocharging synaptic transmission: 12 SNAREpins are required for rapid release of reconstituted synaptic vesicles
Year: 2026
Type: article
Abstract: -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. How SNAREs cooperate to achieve synchronous neurotransmitter release is a long-standing mystery. Rapid release (<7 milliseconds) has been reconstituted from purified synaptic SNAREs, SNARE-assembling chaperones, and calcium ion sensors in a fully-defined, genetically validated system that enables single-molecule counting in docked vesicles before release. SNAREpin complexes (12 ± 0.3) are found in each such ready-release vesicle, suggesting a regular structure. Several genetic conditions (including point mutation of the synaptic vesicle protein Synaptophysin from a Synaptopathy patient and human and mouse disease mutations of the synaptic vesicle protein vesicle-associated membrane protein-2 (VAMP2) reduce the number of SNAREpins to 6 ± 0.3 and result in profoundly delayed release over 0.1 to 1 seconds. Omitting Synaptophysin, whose hexamers preassemble 12 copies of VAMP2, also yields ~6 SNAREpins and delays release.
Source: Science Advances
Authors: Manindra Bera, Atrouli Chatterjee, Amit Koikkarah Aji, Aniruddha Panda, R. Venkat K. Sundaram, Jeff Coleman, Reza Maroofian, Vincenzo Salpietro, Abhijith Radhakrishnan, Sudhanshu Gautam, Kirill Grushin, Matthieu Caruel, Henry Houlden, Kallol Gupta, Sathish Ramakrishnan, Frederic Pincet, James E. Rothman
Institutions: Yale University, UCL Queen Square Institute of Neurology, University College London, University of L'Aquila, European Brain Research Institute, Centre National de la Recherche Scientifique, Université Paris-Est Créteil, Laboratoire Modélisation et Simulation Multi-Echelle, Université Paris Cité, Université Paris Sciences et Lettres, École Normale Supérieure - PSL, Sorbonne Université, Laboratoire de Physique de l'Ecole Normale Supérieure
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W7166870663