SP 5 Signalling pathways controlling actin dynamics in adaptive stress responses in the brain underlying neuronal plasticity

Project Leader: Britta Qualmann

Background and previous work
Adaptive responses in neurons require morphological alterations in cell shape controlled by the cortical actin cytoskeleton. The proposed project is built on the identification and initial characterisation of important neuronal signalling mechanisms regulating actin dynamics via the actin nucleator Cobl. Our identification of calmodulin, an important calcium sensor and signaling molecule, as an Ca2+-concentration-dependent interaction partner for Cobl unveils a molecular mechanism, which interconnects neuronal calcium signalling to actin-driven neuronal arborisation underlying neuronal network formation.

Specific aims and working programme
The proposed project will follow the exciting working hypothesis that Ca2+-concentration-dependent complex formation of Cobl with calmodulin revealed in the first funding period may represent a molecular mechanism for interconnecting signalling processes to structural organization and plasticity in neurons.
We therefore aim at investigating the effects of Ca2+-mediated signalling on cytoskeletal-driven structural and functional adaptive responses in neurons under physiological as well as excitotoxic conditions in a dose- and time-course dependent manner. Our studies shall unveil the exact signalling cascades involved and their temporal coordination during adaptive stress responses in dendritic arborisation as well as synapse formation and plasticity. The recent successful generation of Cobl-deficient mice in our group will furthermore allow for addressing such neurohormetic signalling responses mediated by actin cytoskeletal changes in an animal model.