AnkyrinG: A molecular determinant of axo-dendritic polarity

• Applicant: Professor Dr. Christian Schultz
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 72373762

Neurons develop and maintain two distinct types of processes: axons and dendrites. Little is known about the molecular mechanisms that underlie the development and maintenance of axodendritic polarity in vivo. Previous in vitro studies have indicated that a membrane-associated diffusion barrier, localized in the axon initial segment (AIS), contributes to the maintenance of axo-dendritic polarity. To address this issue, we have obtained mice with a cerebellum-specific loss of ankyrinG, a crucial component of the AIS-specific diffusion barrier. Preliminary data indicate that Purkinje cell axons of ankyrinG-/- mice exhibit features of axons and dendrites. These axo-dendritic hybrids - denoted as “axodendrites” – develop cytoplasmic protrusions closely resembling dendritic spines. Similar to their dendritic counterparts, these axodendritic spines are enriched with postsynaptic proteins and contacted by glutamatergic terminals. Moreover, pronounced Purkinje cell loss was noted in cerebellar regions with a high prevalence of axodendrites. The proposed studies will serve to (I) further define molecular, ultrastructural, and functional characteristics of axodendrites, (II) analyse mechanisms of cell death in ankyrinG-/- mice, (III) crossbreed ankyrinG-/- mice with mice that express green fluorescent protein in Purkinje cells and (IV) perform dynamic in vitro imaging of developing axodendrites.

• DFG Programme: Research Grants