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Projects

Our research focuses on mechanisms that control neuronal actin dynamics and on the relevance of actin regulators for mammalian brain development and function.

  • Structure and function of excitatory synapses

    By exploiting gene-targeted mice, we identified actin depolymerizing proteins of the ADF/cofilin family as crucial regulators of synaptic actin dynamics, brain function and behavior (Rust, EMBO J 2010; Görlich, PLoS One 2011; Goodson, PLoS Genetics 2012; Wolf, Cereb Cortex 2015; Zimmermann, Biol Psychiatry 2015; Rust, Cell Mol Life Sci 2015; Sungur, Front Behav Neurosci 2018). Currently, we search for proteins that control and/or interact with ADF/cofilin in excitatory synapses. We identified cyclase-associated protein 2 (CAP2) - an actin-binding protein that we implicated in myofibril differentiation during skeletal muscle development (Kepser, Proc Natl Acad Sci USA 2019) – as a regulator of cofilin1 recruitment into postsynaptic dendritic spines (Pelucchi, Bran Commun 2020). Further, we found i) that CAP1 interacts with cofilin1 to control of dendritic spine morphology (Heinze, Cell Mol Life Sci 2022), ii) that CAP1 is relevant for synaptic plasticity (Heinze, Eur J Cell Biol 2023) and iii) that CAP1 and CAP2 have acquired overlapping functions in regulating maturation of dendritic spines (Schuldt, Cell Mol Life Sci 2024). Currently, we investigate molecular mechanisms that depend on CAP1 and CAP2 in dendritic spines.

  • Mammalian brain development

    We found that the actin regulators CAP1 and Profilin1 are relevant for the development of the mammalian brain. Profilin1 controls glial cell adhesion and radial migration of cerebellar granule neurons (Kullmann, EMBO Rep 2012; Kullman, Neuroscience 2012; Kullmann, Cell Adhes Migr 2015) as well as fate of neural stem cells in the cerebral cortex (Kullmann, Cereb Cortex 2020). Further, we showed i) that CAP1 together with cofilin1 controls actin dynamics in growth cones and that it thereby regulates growth cone motility and function (Schneider, Prog Neuobiol 2021; Schneider, eNeuro 2021; Schneider, Cells 2021) and ii) that CAP1 regulates gene expression in differentiating neurons and the embryonic mouse brain by repressing MRTF-SRF-mediated transcription (Khudayberdiev, Sci Signal 2024). Currently, we investigate molecular mechanisms that depend on CAP1 and profilin1 during brain development.

  • Current funding

    DFG research grant: Actin-dependent mechanisms relevant for cerebellar morphogenesis and medulloblastoma formation

    Research grant from Alzheimer Forschung Initiative: Deciphering an actin-dependent mechanism relevant for Alzheimer’s disease

    DFG research grant: Deciphering the molecular mechanisms of cyclase-associated protein 1 (CAP1) in regulating dendritic spine morphology and structural plasticity