Seminar

Spectraplakins - cytoskeletal integrators with key roles in brain development

Dr. ANDREAS PROKOP

Spectraplakins are large multi-functional cytoskeletal linker molecules. They have crucial cell biological and developmental functions, important for clinically relevant processes such as brain development, brain degeneration, skin blistering and wound healing. A key role of spectraplakins is the regulation of microtubule networks in neurons and non-neuronal cells alike. However, the underlying mechanisms are not understood. We use the Drosophila spectraplakin Short stop (Shot) as a genetically amenable paradigm, focussing on its crucial role in axonal growth. To decipher Shot's neuronal functions, we use genetic manipulations in vivo as well as in our newly established Drosophila primary neuron culture system. This culture system gives unprecedented access to the study of the neuronal cytoskeleton of the fly, most features of which we find to be highly conserved with mammalian neurons. Accordingly, we find that key functions of Drosophila Shot in axonal growth are conserved with mammalian ACF7. Using our cellular models for Drosophila, we are gaining a detailed understanding of the underlying molecular mechanisms. Our deduced functional models set a precedent for the function of spectraplakins in neuronal and non-neuronal contexts alike, and essentially contribute to the principal understanding of cytoskeletal network regulation at the cellular level.