Mitarbeiter im Fachbereich Biologie
| Püschel, Andeas, Prof. Dr. rer. nat. |
| Abteilung Molekularbiologie Institut für Molekulare Zellbiologie Westfälische Wilhelms-Universität Schlossplatz 5 48149 Münster Germany Tel: + 49 - 251 - 83 - 23841 Fax: + 49 - 251 - 83 - 24723 E-mail: apuschel  www.uni-muenster.de/Biologie.AllgmZoo/ |
| wissenschaftlicher Werdegang |
| - Studium der Biologie: Universität Bonn und Heidelberg - Promotion: Universität Heidelberg; MPI f. biophysikalische Chemie, Göttingen - Postdoctoral research associate: University of Oregon, Institute of Neuroscience, Eugene (Oregon, USA) - Gruppenleiter am MPI für Hirnforschung, Frankfurt - Habilitation in Biochemie: Universität Frankfurt - Professor für Molekularbiologie an der WWU Münster |
| Lehrschwerpunkte |
| Molekular - und Zellbiologie Molekulare Genetik Neurobiologie |
| Forschungsschwerpunkte |
| Entwicklung des Nervensystems Axonale Wegfindung Entwicklung der neuronalen Polarität |
| Ausgewählte Projekte |
| Development of neuronal polarity (Funding: SPP 1111, GRK 1050) The establishment of a polarized morphology and the functional specialization of different cellular compartiments are essential steps in the differentiation of neurons. However, the initial signals that establish a cellular asymmetry and the pathways that subsequently translate this asymmetry into the development of multiple dendrites and a single axon are largely unknown. We use primary cultures of dissociated hippocampal neurons as a model system to elucidate the molecular mechanisms that establish the asymmetric organization of cellular structures. We are investigating the role of different GTPases in the establishment of neuronal polarity to understand the initial events that determine which neurite becomes the axon. Our results show that the sequential activity of the GTPases Rap1B and Cdc42 is essential for the development of neuronal polarity. Initially, these GTPases are present in all neurites of unpolarized neurons but become restricted to a single neurite of late stage 2 neurons. Cdc42 coordinates the activity of different effectors and Rho-family GTPases to execute a program that results in the differentiation of neurons with molecularly distinct dendrites and axons. Future projects will have to address the following questions: 1) How are GTPases and the Par complex restricted to a single neurite? 2) What are the pathways through which Cdc42 polarizes the cytoskeleton of neurons and specifies axonal identity? 3) What is the role of motor proteins and directed intracellular transport in the polarization of neurons? Molecular analysis of signal transduction pathways involved in the guidance of axons (Funding: SFB 629, SFB 492) The wiring of the nervous system is established through a progressive refinement of the choices made by a growing axon. The growth cone is a highly motile structure at the tip of the axon that integrates the multitude of signals present in its environment and translates these signals into structural changes of the cytoskeleton that determine the rate and direction of extension. The semaphorins represent the largest family of guidance cues identified so far. They function mainly as chemorepellents that direct axons away from tissues marked by their expression, but can also act as chemoattractants in some cases. The repulsive effects of the secreted semaphorins is mediated by a receptor complex that contains Neuropilin-1 (Nrp-1) or Nrp-2 as the ligand-binding subunit and an A-type plexin as the signal transducing subunit. At least two signaling pathways are involved in the response to these semaphorins. One includes the small GTPase Rac and leads to the depolymerization of actin filaments. GTPases act as molecular switches that regulate multiple cellular processes by activating downstream effectors when in the GTP-bound form. We are using a combination of molecular, biochemical, genetic and cell biological methods to understand the role of GTPases in the response to semaphorins in primary neurons and transgenic mice. In addition, we investigate the changes in cytoskeletal dynamics in life growth cones as they respond to Sema3A. |
| ausgewählte Publikationen |
Püschel,
A. W., Adams, R. H.,and Betz, H. (1995). Murine semaphorin D/collapsin
is a member of a diverse gene family and creates domains inhibitory for
axonal extension. Neuron 14, 941 - 948. Schwamborn, J.C., Müller, M., Becker, A.H.M., and Püschel, A.W. (2007). Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. EMBO J., in press. |
| Links |
| celldynamics.uni-muenster.de/ sfb629.uni-muenster.de/ www.uni-muenster.de/Biologie.AllgmZoo/Gruppen/Pueschel/index.html |
| Sonstiges |
| Sprecher des DFG Graduiertenkollegs "Molekulare Zelldynamik" (GRK 1050) |
