Spatial segregation of the membrane domains coupling synaptic vesicle exocytosis and endocytosis. Three-dimensional dual-colour isoSTED nanoscopy of cultured hippocampal synapses showing the localization of the released synaptic vesicle protein Syt1, reclustered at endocytic sites (red) at synapses identified by the pre- and postsynaptic markers RIM1 and RIM2 (RIM) and Homer1 (green); scale bars 1 μm (Klingauf group).
© CiM

A.3: Functional membrane domains in neuronal and non-neuronal compartmentalization

Participants: Jürgen Klingauf, Timo Betz, Carsten Fallnich, Milos Galic, Volker Gerke, Andreas Heuer, Stefan LuschnigMarkus Missler, Hans-Christian Pape, Andreas Püschel, Sebastian Rumpf, Ralf Stanewsky, Timo Strünker, Roland Wedlich-Söldner

Considerable evidence shows that inhomogeneities exist in the lateral distribution of proteins and lipids in biological membranes. The protein/lipid domains affect physical properties of the membrane and enrich supra-molecular complexes to form domains of specific functions. These functional domains play important roles in processes such as signal transduction, membrane trafficking and cell adhesion. However, their nature remains poorly described with respect to size, abundance, composition and dynamics. It is the overall goal of this research project to elucidate general principles of the organization of specific membrane domains. This will first be addressed in neuronal signalling and will encompass synaptic membrane recycling, the establishment of polarity as an important basis for structural plasticity, the formation of transsynaptic complexes, and the postsynaptic clustering of specific ion channels and receptors. Principles and methods derived from these analyses will be applied to other cell systems and cell-cell interactions, for example those between glial and neuronal cells and between endothelial and immune cells. To this end, we will apply and develop high resolution imaging techniques (CARS, Stimulated emission-depletion microscopy - STED, Photo-activated localization microscopy - PALM) for visualization of the temporo-spatial dynamics of functional membrane domains in intact neurons and other cells. This will be complemented by emerging optogenetic approaches to specifically examine such interactions and eventually ‘set’ cells in motion.

Funded Projects

FF-2016-12 – Cyclodextrin based copolymer vesicles for delivery of labeled lipids and other cargo into cells
Principal investigators: Bart Jan Ravoo, Armido Studer, Volker Gerke
Project time: 07/2016 - 06/2017