The Active Zone T-Bar—A Plasticity Module?

Abstract

The synaptic active zone, the site where Ca²⁺-triggered fusion of synaptic vesicles takes place, is commonly associated with protein-rich, electron-dense cytomatrices. The molecular composition and functional role of active zones, especially in the context of vesicular exo- and endocytosis, are under intense investigation. Per se, Drosophila synapses, which display so-called T-bars as electron-dense specializations, should be a highly suitable model system, as they allow for a combination of efficient genetics with ultrastructural and electrophysiological analyses. However, it needed a biochemical approach of the Buchner laboratory to “molecularly” access the T-bar by identification of the CAST/ERC-family member Bruchpilot as the first T-bar–residing protein. Genetic elimination of Bruchpilot revealed that the protein is essential for T-bar formation, calcium channel clustering, and hence proper vesicle fusion and patterned synaptic plasticity. Recently, Bruchpilot was shown to directly shape the T-bar, likely by adopting an elongated conformation. Moreover, first mechanisms that control the availability of Bruchpilot for T-bar assembly were described. This review seeks to summarize the information on T-bar structure, as well as on functional aspects, formulating the hypothesis that T-bars are genuine “plasticity modules.”

Keywords::

• active zone
• Bruchpilot
• Drosophila
• structure-function
• T-bar
• ultrastructure

ACKNOWLEDGMENTS

We would like to thank U. Thomas, R. J. Kittel, and D. Owald for careful reading and comments on the manuscript.

Declaration of interest: The authors are supported by grants from the Deutsche Forschungsgemeinschaft to S. J. Sigrist (Exc257).