Our work focuses on palmitoylation’s role as a “molecular switch” in a CD4+T cell context. As phosphorylation is a well established post-translational molecular switch used by T cells in a number of important cellular events on a seconds timescale, we seek to draw a parallel with palmitoylation on a minutes timescale.
- AG Krause, FMP
- AG Kliche, Otto-von-Guericke-University Magdeburg
- AG Brügger, Universität Heidelberg
Regulation of SH3 domain-containing scaffolds in endocytosis and synaptic vesicle cycling
Fast signaling between neurons is based on the stimulation-evoked release of neurotransmitter molecules into the synaptic cleft. Interaction of these molecules with the receptors of the postsynapse then triggers a new action potential in the neighboring neuron. The release of the neurotransmitter via the exocytosis of synaptic vesicles (SVs) is followed by compensatory endocytic retrieval of the excess vesicular membrane. Newly formed SVs are then clustered in specialized vesicle pools from where they are recruited to the membrane for a new round of release. This repeated sequence of events is referred to as the synaptic vesicle cycle.
In order to sustain synaptic transmission even during phases of high neuronal activity, the individual processes of the synaptic vesicle cycle need to be tightly coupled and regulated in an activity-dependent manner. However, the molecular principles underlying this coupling still remain elusive. Interesting candidates for central regulatory roles in the synaptic vesicle cycle are SH3-domain-containing adaptor and scaffolding proteins such as intersectin 1 (ITSN1), endophilin A1 and SNX9. These primarily endocytic proteins shuttle between the sites of SV exocytosis, endocytosis and clustering and interact with a variety of proteins from all stages of the vesicle cycle via their SH3 domains .