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MedUni Vienna researchers on the trail of memory

(Vienna, 29 Jan. 2010) An important piece of the jigsaw in the study of the molecular mechanisms of memory was able to be identified in the Kiebler working group in the Centre for Brain Research at the Medical University of Vienna: the RNA binding protein "Pumilio2" therefore plays an important role in the regulation of morphology and function of the dendrites and in the storage of information on the synapse. The work of Paolo Macchi, Lucia Schoderböck and John Vessey appeared on 29.01. in the renowned science magazine PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Neurons, the functional units of the human brain, are complex cells with three essential components: the cellular body, an axon and many dendrites. Here the dendrites act as receivers and are sent information via synaptic contacts. Most synapses are on short projections with a mushroom-like form and are distributed evenly along the dendrites. Important biological functions of the nervous system such as learning and memory are associated with the development of a complex dendritic network, the arrangement of new synapses and the more efficient functioning of existing synapses. It is still largely unknown, however, how the nerve cell changes its form especially on the synapses or which molecular factors - proteins and/or nucleic acids - trigger and influence these processes.

Scientists from the laboratory of Michael Kiebler at MedUni Vienna have been able to publish an important contribution in the study of these questions. In an earlier project supported by the Austrian Science Fund FWF, Paolo Macchi and PhD student John Vessey already identified two proteins (Pum1, Pum2) as components in the localisation of RNA in nerve cells. Further cell biological and electrophysiological analyses have now shown that Pum2 contributes both to the development of dendrites and also to the synaptic function in the nerve cells. Pum2 is present especially during dendrite development, but a lack of Pum2 in this phase leads to an increased outgrowth of dendrites from the cellular body. As a result, mature neurons with a lack of Pum2 have a higher amount of dendritic branching, unlike neurons with an overexpression of Pum2 which have a simplified dendritic network. This data indicates that the quantity of Pum2 in the cell regulates the form of the dendrites of this nerve cell and also plays a role later when the synapses arise as Pum2 influences the morphology and function of the dendrites. Finally it was also possible to prove that Pum2 binds specific messenger RNAs (mRNAs) which are important for the neuronal function. Although the experiments indicate that Pum2 suppresses the translation, i.e. the production of proteins from these mRNAs, the question of, "how" and "where" these processes occur is still open and will be the subject of further studies. Here Michael Kiebler says the following: "We hope this approach leads to decisive new insights into the function of individual synapses and how the storage of molecular information on synapses could happen."

The Kiebler Laboratory at MedUni Vienna
The focus of research at the Kiebler Laboratory in the Centre for Brain Research at the Medical University of Vienna is on the localisation of messenger RNAs (mRNAs) in nerve cells. These localised mRNAs contribute to important processes such as the asymmetrical distribution of proteins, formation of cell polarity and local protein synthesis at certain parts of a cell. They therefore play an important role in complex phenomena like synaptic plasticity, learning and memory formation, but have also been associated with many neurological diseases such as fragile X chromosome mental retardation, tauopathies, spinal muscular atrophies and dysmyelination.

The authors
Paolo Macchi joined the group of Professor Kiebler back in 1999 as a postdoctoral fellow (at the time still at the Max Planck Institute for Development Biology in Tübingen, Germany) and in 2005 became head of the group at the Centre for Brain Research. In 2007 Macchi qualified as a Professor of "Neurosciences" at MedUni Vienna. Thanks to his research successes, he recently received a Professorship of Molecular Biology at the University of Trento, Italy, and at the Centre for Integrative Biology he heads the Lab of Molecular and Cellular Neurobiology, where he is the coordinator of the doctoral programme "International Doctorate School in Biomolecular Sciences".

John Vessey has also used his scientific training in Vienna as a springboard. A series of publications in peer-reviewed journals during this period brought him a fellowship at the Canadian "Institute of Health Research". He is currently studying with a lucrative post-doc grant in the laboratory of Freda Miller, one of the "Howard Hughes International Investigators".

Lucia Schoderböck completed her molecular biology studies in Vienna and was already carrying out research in the Centre for Brain Research during her dissertation. She is working on her doctorate in the laboratory of Michael Kiebler and has carried on with and concluded John Vessey's work.

» Original work:
Vessey J.P., Schoderböck L., Gingl E., Luzi E., Riefler J., Di Leva F., Karra D., Thomas S., Kiebler M.A. and Macchi P. (2010) Mammalian Pumilio2 regulates dendrite morphogenesis and synaptic function. PNAS