B4 - Pollerberg

We will focus on the in vivo role of the axonal cell adhesion molecule (CAM) DM-GRASP, its signalling, and its interaction partners/effectors. To study the molecular interactions underlying growth and navigation of axons, we use the chick embryo visual system as a model system in which the behaviour of retinal ganglion cell axons can be observed and manipulated in their histotypic environment. We could previously show that DM-GRASP plays a role for axonal growth, preference, and navigation. We were now able to demonstrate that ubiquitination, endocytosis, and degradation of DM-GRASP in the growth cone regulate its presence in the plasma membrane. The fine-regulated spacing of DM-GRASP could be shown to be crucial for axon extension. We furthermore demonstrated that activation of DM-GRASP triggers the activity of the kinase Erk which is crucial for the endocytosis of DM-GRASP. Moreover, we could show growth cone microtubule dynamics to be regulated by kinases/phosphatases acting on microtubule-associated proteins MAP1B and APC, respectively, which could both be demonstrated to play a role in growth cone steering.
We will continue to study the in vivo relevance of DM-GRASP's balanced presence in the growth cone plasma membrane. For this, we will use techniques interfering with the expression and/or function of DM-GRASP as well as its effectors (overexpression, shRNA and dominant-negative approaches) and study the impact on growth and pathfinding of RGC axons (time lapse analysis, 3D/4D microscopy) in the intact retina in ovo. Also the microtubule-associated proteins mentioned above will be studied for their functions in growth cones navigating in their histotypic environment.

Wir untersuchen auf zellulär-molekularer Ebene, welchen Einfluss das Zelladhäsionsmolekül DM-GRASP im Zusammenspiel mit seinen Interaktionspartnern und Effektoren auf das Wachstum und die Navigation von Axonen hat. Dazu manipulieren wir diese Proteine mit gen- und proteintechnischen Ansätzen, um ihre Funktion zu verstärken bzw. zu inhibieren. Die Auswirkungen dieser Manipulationen auf das Verhalten der Axone in der intakten embryonalen Retina werden durch neueste Mikroskopietechniken untersucht und lassen so Rückschlüsse auf die Rolle von DM-GRASP sowie seinen Partnern und Effektoren im histotypischen Kontext zu.

Own project-related publications since the last application (2005)

Zelina, P., Avci, H. X., Thelen, K., and Pollerberg, G. E. (2005) The cell adhesion molecule NrCAM is crucial for growth cone behaviour and pathfinding of retinal ganglion cell axons. Development 132: 3609-3618

Thelen, K., Wolfram, T., Maier, B., Jährling, J., Tinazli, A., Piehler, J., Spatz, J. P., and Pollerberg, G. E. (2007) Cell adhesion molecule DM-GRASP presented as nanopatterns to neurons regulates attachment and neurite growth. Soft Matter 3: 1486-1491

Koester, M. P., Muller, O., and Pollerberg, G. E. (2007) Adenomatous polyposis coli is differentially distributed in growth cones and modulates their steering. J Neurosci 27: 12590-12600

Hahn, C. M., Kleinholz, H., Koester, M. P., Grieser, S., Thelen, K., and Pollerberg, G. E. (2005) Role of cyclin-dependent kinase 5 and its activator P35 in local axon and growth cone stabilization. Neuroscience 134: 449-465

Own project-related publications prior to 2005

Avci, H. X., Zelina, P., Thelen, K., and Pollerberg, G. E. (2004) Role of cell adhesion molecule DM-GRASP in growth and orientation of retinal ganglion cell axons. Dev Biol 271: 291-305

Mack, T. G., Koester, M. P., and Pollerberg, G. E. (2000) The microtubule-associated protein MAP1B is involved in local stabilization of turning growth cones. Mol Cell Neurosci 15: 51-65

G. Elisabeth Pollerberg

Abt. Entwicklungsneurobiologie

Institut für Zoologie, Universität Heidelberg

Im Neuenheimer Feld 232

69120 Heidelberg

Phone:  06221-546370
Fax:      06221-546375
email:   G.E.Pollerberg(at)urz.uni-heidelberg.de