Medical Scientist-Programm 2019

Thema: "Molecular mechanisms of the Ca2+/Calmodulin-mediated control of actin cytoskeleton-driven neuromorphogenesis processes mediated by the actin nucleator JMY"

Zusammenfassung:
The polar and extremely arborized morphologies that neurons develop are a prerequisite for signal processing in neuronal networks. Their development seems to be promoted by local Ca2+ signals and by actin filament formation. The initial assembly of actin nuclei requires actin nucleators. These components represent prime targets for regulatory mechanisms, as F-actin assembly requires tight temporal and spatial control. We have recently identified the actin nucleator JMY as novel interaction partner for Ca2+-activated calmodulin (CaM) and propose to follow the exciting working hypothesis that JMY/CaM complex formation represents a mechanism for interconnecting signaling processes to structural organization and plasticity in neurons by applying biochemical and cell biological approaches. After revealing the molecular mechanism(s) of the Ca2+/CaM-mediated regulation of JMY we aim at defining the role of JMY in neuronal morphology control and its regulation by Ca2+/CaM. Unraveling the neuronal functions of this machinery for actin nucleation and understanding how it is mechanistically linked to Ca2+/CaM signaling will significantly increase our understanding of cortical actin cytoskeletal processes underlying neuromorphogenesis and the formation of neuronal networks – processes crucial for brain functions of all higher eukaryotes.