Funktionen des zellulären Prion Proteins für die Entwicklung von Zell-Zell Kontakten und Axonwachstum

• Applicant: Professorin Dr. Claudia Stürmer
• Subject Area: Developmental Neurobiology
• Term: from 2009 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 126074341

The GPI-anchored Prion protein (PrP) is well-known since its misfolded conformer is the causative agent of the neurodegenerative diseases in man and animals (such as BSE) - but its physiological function is poorly understood. Our work in zebrafish and cells suggests a role of PrP in cell-cell communication/adhesion and interaction with the cadherin adhesion system. Our results, moreover, show signal transduction by PrP in association with the microdomain scaffolding protein reggie (flotillin) and its signalling partners. Based on these findings we developed the hypothesis that clustering in reggie microdomains allows PrP to transduce signals into the cell and to communicate with the actin cytoskeleton. Here, we aim at understanding the contribution of PrP to cell-cell contact formation in conjunction with reggie and its associates and to the recruitment of cadherins to forming contacts. Both events require actin cytoskeletal reorganisation. We will therefore analyse the contribution of specific adapter and signal transduction molecules such as CAP, afadin, src tyrosine kinases, p120ctn, Rho-GTPases etc. to cell contact formation, regulation of the actin cytoskeleton and neurite growth. Our analysis will include determination of PrP-reggie function in filopodia and lamellipodia which establish first contacts between cells and which may recruit p120 and cadherins for cell contact maturation.

• DFG Programme: Research Grants