Research Topics of the Haucke Group

Our lab is focussed on the molecular mechanisms of endocytic and endosomal membrane traffic with a particular interest in clathrin-mediated endocytic events at neuronal synapses. We also study the role of clathrin adaptors, their associated factors, and of phosphoinositide lipids in intracellular traffic within the trans-Golgi-network/ endosomal system. Over the years we have largely dealt with three interrelated questions:

1. Which role do membrane lipids play in endocytic events at synapses as well as in endocytosis in non-neuronal cell types?

2. How are transmembrane cargo proteins, specifically pre- and postsynaptic proteins recognized by the endocytic machinery and how is this regulated at the molecular level?

3. How are vesicle- or tubule-mediated dynamics coupled to cytoskeletal elements?

Visualization of detergent-resistant synaptic membranes in primary hippocampal neurons using the raftophile cholera toxin B (green). Labelled cholera toxin B is shown to co-localize with the presynaptic vesicle marker protein synaptotagmin 1 (red). Source: Jia et al., (2006)

Using a combination of fluorescence-based imaging approaches including live cell confocal and total internal reflection (TIRF) microscopy together with in vivo systems we have gained a number of important and novel insights into the interplay between membrane-associated proteins and lipids in clathrin-dependent endocytosis, synaptic vesicle cycling, and TGN/ endosomal membrane dynamics. Research from our laboratory resulted in the discovery of important regulatory pathways that contribute to the initial stages of clathrin-coated pit assembly and to the synthesis of a subpool of PIP2 dedicated to clathrin-mediated endocytosis. A number of years ago we have identified stonin 2 as the first endocytic sorting adaptor dedicated to clathrin-mediated synaptic vesicle recycling. In addition we have been able to track down novel types of endocytic AP-2 interaction motifs found in both pre- and postsynaptic membrane proteins. More recently, the lab has unravelled a molecular mechanism that couples dynamin-mediated membrane fission to membrane deformation by BAR domain proteins such as syndapin.

Similar principles govern membrane traffic at the TGN/ endosomal interface.

Research areas of our lab

• Clathrin-mediated endocytosis
• Membrane traffic at the TGN/ endosomal interface
• Phosphoinositides in membrane traffic
• Mechanisms of synaptic vesicle recycling