Results Synaptic interactome

In order to develop effective therapies for synaptic diseases it is imperative that the architecture and dynamics of the synaptic interactome are revealed and the disease-causing changes in the interactome are identified. The key objective of this Research Team was to provide a qualitative/quantitative description of the (extra-) synaptic interactome and to generate quantitative dynamical models of selected ‘hubs’, such as the AMPA receptor (AMPAR).

Results

We identified major interactors of the AMPA‐type glutamate receptor using mass spectrometric analysis and we focused on the function of one of these, i.e., Pancortin/olfactomedin. We have established extraction and analysis methods for ECM and ECM‐associated molecules from acute hippocampal slices and performed candidate and MS/MS approaches to identify ECM core components and ECM‐associated molecules In addition, we have identified a novel interaction between the scaffolding molecule AKAP79/150, which is a key regulator for neuronal signaling and the postsynaptic calcium binding protein caldendrin. The students involved in WP2 presented and discussed the data obtained in this workpackage in the final annual meeting at RIKEN, Yokohama.

Publications

  • Gorny, X., Mikhaylova, M., Seeger, C., Reddy, P.P., Reissner, C., Schott, B.H., Helena Danielson, U., Kreutz, M.R. & Seidenbecher, C. (2012) AKAP79/150 interacts with the neuronal calcium‐binding protein caldendrin. J Neurochem, 122, 714‐726.
  • Hallermann, S., Fejtova, A., Schmidt, H., Weyhersmuller, A., Silver, R.A., Gundelfinger, E.D. & Eilers, J. (2010) Bassoon speeds vesicle reloading at a central excitatory synapse. Neuron, 68, 710‐723.
  • Seeger, C., Gorny, X., Reddy, P.P., Seidenbecher, C. & Danielson, U.H. (2012) Kinetic and mechanistic differences in the interactions between caldendrin and calmodulin with AKAP79 suggest different roles in synaptic function. Journal of molecular recognition: JMR, 25, 495‐503.
  • Valenzuela JC, Heise C, Franken G, Singh J, Schweitzer B, Seidenbecher CI, Frischknecht R. Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity. Philos Trans R Soc Lond B Biol Sci. 2014 Oct 19;369 www.ncbi.nlm.nih.gov/pubmed/25225099

Poster Abstracts

  • AKAP79/150 and Caldenrin – a New Relationship in the Synapse. X. Gorny, M. Mikhaylova, B. Schott, M. Kreutz, C. Seidenbecher. 9th Göttingen Meeting Of The German Neuroscience Society March 23 ‐ 27, 2011 Abstr. Nr. T7‐4a.
  • Role Of ADAMTS4 and Processing of Brevican in Synaptic Plasticity. J.C. Valenzuela Macaya, C. Heise, G. Franken, E.D. Gundelfinger, C.I. Seidenbecher, R. Frischknecht. 8th Fens Forum Of Neuroscience 2012 July 14‐18 2012, Barcelona, Spain. Abstr. Nr. 2638, P. 473
  • Decreased Brevican Levels are Associated with Increased Expression of Cocaine‐Induced
    Conditioned Place Preference. B.R. Lubbers, M.C. Van Den Oever, R. Frischknecht, E.D.
    Gundelfinger, C.I. Seidenbecher, A.B. Smit, S. Spijker. 8th Fens Forum Of Neuroscience 2012 July 14‐18 2012, Barcelona, Spain. Abstr. Nr. 956, P. 634
  • Research teams

    To reach its objectives, the BrainTrain research program is composed of 5 scientific Research Teams, see list below, with 3 trainees each.
  • Genetics of the brain

    The increasing prevalence for neurodegenerative disease in our aging population poses a growing problem for healthcare.
    >Read more
  • The synaptic interactome

    Many brain disorders are to be considered 'synaptic diseases" or 'synaptopathies' and cellular function of synapses.
    >Read more
  • Functional genomic of the synapse

    The synapse is a specialized structure between two neurons at which basal neuronal communication takes place.
    >Read more
  • Synaptic plasticity

    In neuropsychiatric disorders associated with reduced cognitive abilities, such as age-related cognitive decline, but also mental retardation, the ability of synapses to alter their strength is strongly affected.
    >Read more
  • Transmission and behavioral function

    The etiology of many disorders including age-related cognitive decline and neurodegenerative disorders such as dementia and Parkinson’s disease is still poorly understood.
    >Read more