Projektdaten

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JMY, a cytoskeletal effector leading to actin filament formation, as target for Calcium/CaM signaling in neuronal cells

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Changes in actin cytoskeletal architecture and modulations of actin dynamics play an important role in structural organization and functional adaptations of subcellular compartments, organelles and entire cells in multicellular organisms. Neuronal cells also rely on cytoskeletal processes for establishment of polarity, formation of growth cones, and neurite extension during differentiation and development. All of these processes require tight temporal and spatial control of actin filament formation. The initial assembly of G-actin into actin nuclei for further spontaneous actin polymerization is kinetically not favored but requires cellular components that actively overcome this kinetic barrier. These include: i) the Arp2/3 complex, ii) formins, and iii) WH2 domain containing actin nucleators e.g. including Cobl, JMY and Spire. These actin nucleators thus represent prime targets for regulatory mechanisms. Recent works has demonstrated that Ca2+/CaM signaling is an important mechanism for control of actin filament-promoting factors in neurons and Ca2+/CaM signaling seems to be a general principle in early neuronal development. JMY nucleates actin and in addition promotes actin nucleation by the Arp2/3 complex. Our comprehensive studies aimed at unraveling the detailed molecular mechanisms, by which JMY controls the actin cytoskeleton. This work will significantly increase our understanding of cortical actin cytoskeletal processes underlying neuromorphogenesis and the formation of neuronal networks – prerequisites for proper brain development and neuronal cell-cell communication.