cryo-electron tomography; SNARE; synapse; liposomes; synaptosome; CEMOVIS; PC12 cells; vitreous sections; neurotransmitter release; membrane fusion
Iacovache Ioan, De Carlo Sacha, Cirauqui Nuria, Dal Peraro Matteo, van der Goot F Gisou, Zuber Benoît (2016), Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process., in Nature communications
, 7, 12062.
Ruegsegger Céline, Stucki David M, Steiner Silvio, Angliker Nico, Radecke Julika, Keller Eva, Zuber Benoît, Rüegg Markus A, Saxena Smita (2016), Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology., in Neuron
, 89(1), 129-46.
Trikin Roman, Doiron Nicholas, Hoffmann Anneliese, Haenni Beat, Jakob Martin, Schnaufer Achim, Schimanski Bernd, Zuber Benoît, Ochsenreiter Torsten (2016), TAC102 Is a Novel Component of the Mitochondrial Genome Segregation Machinery in Trypanosomes., in PLoS pathogens
, 12(5), 1005586-1005586.
Studer Daniel, Klein Alycia, Iacovache Ioan, Gnaegi Helmut, Zuber Benoît (2014), A new tool based on two micromanipulators facilitates the handling of ultrathin cryosection ribbons., in Journal of structural biology
, 185(1), 125-8.
Gao Min, Kim Young-Ki, Zhang Cuiyu, Borshch Volodymyr, Zhou Shuang, Park Heung-Shik, Jákli Antal, Lavrentovich Oleg D, Tamba Maria-Gabriela, Kohlmeier Alexandra, Mehl Georg H, Weissflog Wolfgang, Studer Daniel, Zuber Benoît, Gnägi Helmut, Lin Fang (2014), Direct observation of liquid crystals using cryo-TEM: Specimen preparation and low-dose imaging., in Microscopy research and technique
Daffe Mamadou, Zuber Benoît (2014), The Fascinating Coat Surrounding Mycobacteria, in Remaut Han (ed.), Caister Academic Press, Norfolk, 179.
Voigt Tilman, Zuber Benoît, Gawatz Gerlinde, Herrmann Gudrun (2013), Implementation of a virtual correlative light and transmission electron microscope., in Microscopy research and technique
Zuber Benoît, Unwin Nigel (2013), Structure and superorganization of acetylcholine receptor-rapsyn complexes, in PNAS
Wolfmeier Heidi, Radecke Julika, Schönauer Roman, Köffel René, Babiychuk Victoria, Drücker Patrick, Hathaway Lucy, Mitchell Tim, Zuber Benoît, Draeger Annette, Babiychuk Eduard, Active release of pneumolysin prepores and pores by mammalian cells undergoing a Streptococcus pneumoniae attack, in BBA - General Subjects
Stucki David M, Ruegsegger Céline, Steiner Silvio, Radecke Julika, Murphy Michael P, Zuber Benoît, Saxena Smita, Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ., in Free radical biology & medicine
The objective of my laboratory is to understand the mechanisms underlying Ca2+-dependent membrane fusion, a process at the heart of critical biological processes such as synaptic transmission and hormone release. Cytoplasmic vesicles fuse with the plasma membrane in response to an increased cytoplasmic Ca2+ concentration and release their content outside the cell; a process also known as exocytosis. Defects in this process have been linked to severe diseases such as Parkinson’s disease, tetanus, and diabetes. Ca2+-dependent membrane fusion has been extensively studied by a variety of approaches both in vivo and in vitro but several steps remain unclear. Our structural analysis of synapses both by cryo-electron microscopy of vitreous sections (CEMOVIS) and, in collaboration with V. Lucic and W. Baumeister’s group, by cryo-electron tomography (cryoET) has demonstrated the superiority of these techniques over conventional electron microscopy techniques. My laboratory will develop new methods for studying the fast process of Ca2+-dependent membrane fusion. First, we will use a novel cryoET approach to describe the sequence of structural changes occurring milliseconds after Ca2+ influx in isolated synapses with nanometre-resolution. Second, we will adapt a cell-free system of Ca2+-dependent exocytosis to cryoET. In this setup, the plasma membrane of neuroendocrine cells is purified along with docked, fusion-competent, secretory vesicles. There we will not only observe structural changes induced by Ca2+ rise but also localise the proteins involved in membrane fusion by specifically labelling them. Third, we will use an in vitro reconstitution system of Ca2+-dependent membrane fusion and combine it with cryoET. This will give us new ways of assessing the role of specific proteins in the process of bringing membranes together. Finally, we will study Ca2+-dependent membrane fusion in intact cells by cryoET of vitreous sections after improving high pressure freezing of adherent cells. Overall, our work will provide a better understanding of Ca2+-dependent membrane fusion and will serve as a structural framework for refinement of its model.