Prof. Dr. Peter Sonderegger

 

Main Goals, Keywords

Molecular mechanisms of synaptic function and plasticity. Role of extracellular proteolysis at the synapse in the regulation of synaptic structure, function, and plasticity. Role of vesicle transport to and from the synapse in the regulation of synaptic structure, function, and plasticity.

Keywords: Neural plasticity, synaptic plasticity, synapse, proteases, proteolysis, presynaptic terminals, neuroserpin, Neurotrypsin, Calsyntenin-1, Calsyntenin-1, Calsyntenin-3, postsynaptic membrane, postsynaptic density, dendritic spines, spine apparatus, vesicular transport, Kinesin-1, kinesin-light chain, motor proteins, cargo-docking protein)

Group Members

1 professor, 1 lab manager, 2 senior postdocs, 5 postdocs, 10 graduate students, 1 secretary

Previous and Current Research

Our research aims at understanding the molecular mechanisms of synaptic plasticity. In particular, we study the role of extracellular proteolysis and vesicular trafficking at synapses in the regulation of their structure, function, and modification. Our interest in these synaptic processes has been raised by the discovery of several novel proteins in our lab: (1) Neurotrypsin, a synaptic protease; (2) Neuroserpin, an axonally secreted serine protease inhibitor; and (3) Calsyntenin-1, Calsyntenin-2, and Calsyntenin-3, a family of transmembrane proteins of the postsynaptic membrane.

Neurotrypsin is an important regulator of adaptive synaptic processes. Deficient Neurotrypsin in humans results in a severe mental retardation. We investigate Neurotrypsin using a broad range of experimental approaches ranging from enzymological and protein chemical studies in vitro to studies on cultured neurons and to the elucidation of its in vivo function in transgenic and knock-out mice.

The Calsyntenin family of postsynaptic membrane proteins comprises Calsyntenin-1, -2, and -3. These proteins are involved in intracellular vesicular transport. During neural development, the Calsyntenins mediate vesicular transport along axonal microtubules by acting as a cargo-docking protein for Kinesin-1 motors. In the adult CNS the Calsyntenins are localized to the postsynaptic membrane and the subsynaptic vesicular organelles. Their role for vesicular transport to and from the postsynaptic membrane is a major topic of current resarch in our lab.

 

Techniques and Equipment

Neuronal cell culture, neurite growth assays, compartmental cell culture system, Laser Tweezers.
Protein purification, protein chemistry, protein mutagenesis, protein microsequencing, Western blot analysis, two-dimensional SDS-PAGE, analysis of protein-protein interactions.
Proteomics, Genomics.
Cloning of cDNAs and genes, prokaryotic and eukaryotic protein expression, promotor analysis, search for protein ligands by eukaryotic expression cloning, gene transfer by adenoviral vectors, generation of GFP-tagged proteins and their use in cell biological assays.
Gene overexpression in transgenic mice, Cre-lox based conditional gene overexpression, gene inactivation (knock-out) by homologous recombination, conditional knock-out, knock-in technology for the study of in vivo effects of genetic mutations.
Immunohistochemistry, immuno-EM, in situ hybridization, confocal microscopy, life imaging microscopy.

Selected Publications

• Dityatev, A., Schachner, M., Sonderegger, P. The dual role of the extracellular matrix in synaptic plasticity and homeostasis. Nat Rev Neurosci. Oct 14 (2010).
  
• Steuble, M., Gerrits, B., Ludwig, A., Mateos, J.M., Diep, T.M., Tagaya, M., Stephan, A., Schätzle, P., Kunz, B., Streit, P., Sonderegger, P. Molecular characterization of a trafficking organelle: Dissecting the axonal paths of calsyntenin-1 transport vesicles. Proteomics. Sep 9 (2010).
  
• Matsumoto-Miyai, K., Sokolowska, E., Zurlinden, A., Gee, C.E., Lüscher, D., Hettwer, S., Wölfel, J., Ladner, A.P., Ster, J., Gerber, U., Rülicke, T., Kunz, B., Sonderegger, P. Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage. Cell. Mar 20; 136(6): 1161-71 (2009).

Selected Lectures, Seminars or Colloquia

BIO 344 Development of the nervous system: Synapse formation and synapse editing
Advanced Courses in Neurosciences (ZNZ PhD program)

Funding

Swiss National Science Foundation, NCCR "Neural plasticity and repair", Transregio-SFB Konstanz-Zurich, EU-Network APOPIS

URL

http://www.bioc.uzh.ch/index.php?id=67