SciLifeLab The Svedberg seminar series 2013-11-25
Institut für Physiologie, Universität des Saarlandes, Homburg, Germany
Jens Rettig is interested in the molecular mechanisms underlying regulated exocytosis. His lab investigates this topic by a spectrum of high-resolution imaging and electrophysiological methods in combination with structure/function studies in two model systems, adrenal chromatin cells and cytotoxic T lymphocytes.
“The other synapse: calcium-dependent exocytosis in the immune system”
Ca2+-dependent exocytosis of signalling substances is one of the most important tasks of any cell in our body. The most heavily studied exocytic event takes place at synapses between neurons where neurotransmitters are released from synaptic vesicles. However, the molecular mechanism of neurotransmitter release is difficult to study due to technical reasons like synapse size and speed.
Cytotoxic T lymphocytes (CTLs) are part of the adaptive immune system and kill target cells by formation of an immunological synapse (IS) followed by the directed release of toxic substances from lytic granules. Interestingly, a number of proteins like Munc13, Munc18 or syntaxin, which have been shown to be involved in neurotransmitter release, are instrumental for lytic granule release as well.
We have investigated the molecular mechanism of IS formation and function in primary CTLs from mouse and human. Knockout/knockdown approaches have been combined with high-resolution fluorescence microscopy, electron microscopy and functional assays to elucidate the contribution of several key proteins. In addition, molecular states preceding LG fusion could be resolved by total internal reflection fluorescence microscopy (TIRFM) in combination with whole-cell patch-clamp recordings. I will present the latest findings from our lab which identify parts of the molecular machinery that is required for sequential fusion events occuring at the IS.
Host: Bryndis Birnir