Head of the Institute Functional Cell Morphology
Universitätsstraße 1 40225 Düsseldorf
We are interested in the formation and remodeling of synaptic connections. Once formed, synapses are not static but are reorganized throughout life. The reorganization of synapses is generally accompanied by changes in electrical activity, occurring e.g. during learning and memory processes or postembryonic growth programs. Which molecules regulate these activity-induced structural changes? We use the Drosophila neuromuscular junction (NMJ) as a model system to identify conserved regulators of synaptic remodeling, as it shares important chemical and structural features with excitatory synapses in the vertebrate brain. In large-scale mutagenesis screens we isolate mutations that interfere with the adaptation of the size of NMJs, i.e. the number of release sites, to the contractile strength of muscles.
Mutations inhibiting synaptic adhesion proteins or the synaptic cytoskeleton interfere with the assembly and organization of NMJs in Drosophila. Currently, we are studying the transsynaptic Neurexin/Neuroligin complex. Neurexins and Neuroligins interact across the synaptic cleft and organize a synaptic scaffold that precisely aligns presynaptic transmitter release sites and postsynaptic receptor fields.
In another project, we are examining the functions of the Ankyrin/Spectrin-based synaptic cytoskeleton. During muscle contractions, NMJs are exposed to tremendous mechanical strain. NMJs lacking functional support of the synaptic cytoskeleton can no longer be stabilized and degenerate over time. Since these proteins are highly conserved in vertebrates we hope that our results will also shed some light on the mechanisms of neurodegenerative diseases in humans.
- Niehues, S., Bussmann, J., Steffes, G., Erdmann, I., Köhrer, C., Sun, L., Wagner, M., Schäfer, K., Wang, G., Koerdt, S.N., Stum, M., RajBhandary, U.L., Thomas, U., Aberle, H., Burgess, R.W., Yang, X.L., Dieterich, D. and Storkebaum, E. (2015). Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases. Nat. Commun. 6, 7520. PubMed
- Stephan, R., Goellner, B., Moreno, E., Frank, C.A., Hugenschmidt, T., Genoud, C. Aberle, H. and Pielage J. (2015). Hierarchical microtubule organization controls axon caliber and transport and determines synaptic structure and stability. Dev. Cell 33, 5-21. PubMed
- Aberle, H. (2013). Redox switch for actin. Nat. Cell Biol. 15, 1403-1404. PubMed
- Owald, D., Khorramshahi, O., Gupta, V.K., Banovic, D., Depner, H., Fouquet, W., Wichmann, C., Mertel, S., Eimer, S., Reynolds, E., Holt, M., Aberle, H. and Sigrist, S.J. (2012). Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly. Nat. Neurosci. 15, 1219-1226. PubMed
- Banovic, D., Khorramshahi, O., Owald, D., Wichmann, C., Riedt, T., Fouquet, W., Tian, R., Sigrist, S. J., Aberle, H. (2010). Drosophila Neuroligin 1 promotes growth and postsynaptic differentiation at glutamatergic neuromuscular junctions. Neuron 66:724-738. PubMed
- Siebert, M., Banovic, D., Goellner, B., Aberle, H. (2009). Drosophila motor axons recognize and follow a Sidestep-labeled substrate pathway to reach their target fields. Genes & Dev. 23:1052-1062. PubMed
- Koch, I., Schwarz, H., Beuchle, D., Goellner, B., Langegger, M., Aberle, H. (2008). Drosophila ankyrin 2 is required for synaptic stability. Neuron 58:210-222. PubMed
- Beuchle, D., Schwarz, H., Langegger, M., Koch, I., Aberle, H. (2007). Drosophila MICAL regulates myofilament organization and synaptic structure. Mech. Dev. 124:390-406. PubMed
- Meyer, F., Aberle, H. (2006). At the next stop sign turn right: the metalloprotease tolloid-related 1 controls defasciculation of motor axons in Drosophila. Development 133:4035-4044. PubMed
- Mahr, A., Aberle, H. (2006). The expression pattern of the Drosophila vesicular glutamate transporter: A marker protein for motoneurons and glutamatergic centers in the brain. Gene Expr. Patt. 6:299-309. PubMed
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