Research

Since 2001, Prof. Dr. Rizzoli focused his work on mechanisms of pre-synaptic function, especially on synaptic vesicle recycling. Over the years, we have identified and developed a new concept of neurotransmitter release, in which a small number of “perfect” synaptic vesicles participate in most synaptic release events. These vesicles are mobile and therefore are always able to move towards the release sites (active zones), while all other vesicles are immobile, and fuse only rarely. We have described various elements of this model (Rizzoli and Betz, Science, 2004; Westphal et al., Science, 2008; Kamin et al., Biophys J, 2010; Hoopmann et al., PNAS, 2010; Wilhelm et al., Nat Neurosci, 2010), and also extended it to most known synaptic preparations in important reviews of the field (Rizzoli and Betz, Nat Rev Neurosci, 2005; updated in Denker and Rizzoli, Front Synaptic Neurosci, 2010). Recently, we demonstrated this concept in synapses of behaving animals, in what is the first study of vesicle function in vivo (Denker et al., PNAS, 2011a; Denker et al., PNAS, 2011b). In addition to the synaptic vesicle studies, I have applied the membrane trafficking tools I developed to other systems such as endosomal sorting (for example Bethani et al., EMBO J, 2007; Barysch et al., PNAS, 2009).

In a second perspective, we have a strong interest in developing microscopy techniques, most importantly by applying super-resolution microscopy to biological questions. Focusing on stimulated emission depletion (STED) microscopy, we provided the first true biological application of the technique (Willig et al., Nature, 2006) and the first live-imaging application (Westphal et al., Science, 2008), besides participating in other efforts such as the first multi-color super-resolution applications (Donnert et al., Biophys J, 2007).

Our laboratory has a dual focus – high-end imaging and cutting edge research in synaptic physiology. All projects make use of advanced imaging techniques, including STED and electron microscopy. The ultimate goal of our work is to understand the functional organization of the cell – the connection between the topological distribution of cellular elements (proteins or organelles) and their function. We currently focus on the presynaptic compartment, whose relative simplicity and well understood function render such studies more feasible.

Briefly, most proteins investigated so far by high resolution imaging form super-molecular assemblies or clusters. The reasons why they do so are complex, with no general explanation available, especially as the location of the clusters often does not correlate with the protein function. For example, fusion proteins involved in synaptic vesicle exocytosis can be found in clusters everywhere on the plasma membrane, even in places where there are no vesicles. Having an excess number of copies in a cluster is not limited to proteins: synaptic vesicles can be found clustered in immense numbers, especially in neuromuscular junctions, with few explanations available as to the functional relevance of most vesicles (for example, from the ~500,000 vesicles in the frog cutaneous pectoris neuromuscular junction, only ~250 vesicles are used for one action potential).

Thus, the functional organization of many synaptic (or cellular) elements is poorly understood. To solve this type of question, we combine imaging, biochemistry and biophysics to determine the amount of free molecules, of molecules found in clusters, as well as their exchange rates. We then compare all of these values to the numbers of molecules used in function. We termed this approach stoichiometric biology (Lang and Rizzoli, 2010), and we apply it to study both protein clusters and organelle (vesicle) organization. We have recently published the first demonstration of this approach, proposing a novel function for the clusters of synaptic vesicles, in buffering soluble synaptic proteins (Denker et al., 2011b).

Imprint | Disclaimer

Published by
Institute of Neuro- & Sensory Physiology
Humboldtallee 23
37073 Göttingen
Phone  +49 551 395912
Fax  +49 551 3966031
e-mail  rsommer1(at)gwdg.de
URL  http://www.neuro-physiol.med.uni-goettingen.de

 

Director
Prof. Dr. Silvio O. Rizzoli

 

Design and technical realisation
Christian Bertram
Peter Funk

 

 

 

Disclaimer

 

Liability for Content
We make every effort to keep the information on our Web site current, but accept no liability whatsoever for the content provided. Pursuant to §7 par. 1 of TMG (German Tele-Media Act), the law limits our responsibility as a service provider to our own content on these Web pages.

According to §§8 to 10 of TMG, we are not obligated to monitor third party information provided or stored on our Web site. However, we shall promptly remove any content upon becoming aware that it violates the law. Our liability in such an instance shall commence at the time we become aware of the respective violation.

Liability for Links
Our site contains links to third-party Web sites. We have no influence whatsoever on the information on these Web sites and accept no guaranty for its correctness. The content of such third-party sites is the responsibility of the respective owners/providers.
At the time third-party Web sites were linked to ours, we found NO GROUNDS WHATSOEVER of any likely contravention of the law. We shall promptly delete a link upon becoming aware that it violates the law.

Copyrights
The content and works provided on these Web pages are governed by the copyright laws of Germany. Duplication, processing, distribution, or any form of commercialization of such material beyond the scope of the copyright law shall require the prior written consent of its respective author or creator.

Data Protection
Please be aware that there are inherent security risks in transmitting data, such as e-mails, via the Internet, because it is impossible to safeguard completely against unauthorized access by third parties. Nevertheless, we shall safeguard your data, subject to this limitation. In particular, personal information will be transmitted via the Internet only if it does not infringe upon third-party rights, unless the respective party has given its prior consent in view of such security risks. Accordingly, as the Web site provider, we shall not be held liable for any damages incurred as a consequence of such security risks or for any related acts of omission on our part.

We oppose the use of any available contact information by a third party for sending unsolicited advertisements. As the Web site provider, we reserve the express right to take legal action against unsolicited mailing or e-mailing of spam and other similar advertising materials.

source: BSP Rechtsanwälte;  translation: Twigg’s Translations