Institutt for biomedisin

BBB seminar: Tobias M. Böckers

Synapses in health and disease


Tobias M. Böckers
Institute for Anatomy and Cell Biology, Ulm University, Germany

Neurons in the central nervous system (CNS) communicate mainly via specialized excitatory and/or inhibitory contact sites called synapses. It has become evident over the last decades that neurodegenerative disorders as well as neuropsychiatric diseases might at least in part be caused by specific alterations at synaptic sites leading to the new expression “synaptopathies”. Our lab has been working on excitatory synapses for a long time and has especially identified proteins of the postsynaptic density (PSD). Moreover, we are characterizing synaptic plasticity in a set of clinically relevant model systems using in vivo (mouse/rat) and in vitro models (primary culture, iPSC derived neurons). One family of proteins that has been extensively characterized is the ProSAP/Shank proteins that act as a “master-organizer” of the PSD. These proteins were found to be “autism genes” since heterozygous mutations lead to familiar forms of autism. In the seminar I will touch on the general molecular structure of excitatory synapses and allude to some synaptopathies related especially to Shank proteins.

Selected references:

  1. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, Bieth E, Rogé B, Héron D, Burglen L, Gillberg Ch, Leboyer M, Bourgeron Th. Mutations of the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics 2007; 39:25-27
  2. Grabrucker A, Knight MJ, Proepper CH, Bockmann J, Joubert M, Rowan M, Nienhaus UG, Garner C, Bowie J, Kreutz MR, Gundelfinger ED, Boeckers TM. Concerted action of Zinc and ProSAP/Shank in synaptogenesis and synapse maturation. EMBO J 2011; 30:569-581
  3. Schmeisser MJ, Ey E, Wegener St, Kuebler A, Bockmann J, Shiban E, Spilker C, Balschun D, Skryabin BV, tom Dieck S, Smalla KH, Montag D, Leblond C, Faure P, Torquet N, Le Sourd AM, Stempel V, Shoichet S, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger ED and Boeckers TM. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 2012; 486:256-260
  4. Peter S, Ten Brinke MM, Stedehouder J, Reinelt CM, Wu B, Zhou H, Zhou K, Boele HJ,  Kushner SA, Lee MG, Schmeisser MJ, Boeckers TM, Schonewille M, Hoebeek FE, De Zeeuw CI. Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice. Nature Commun 2016; 7:12627

Chairperson: Petri Kursula <petri.kursula@uib.no>, Department of Biomedicine