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Mutual functional dependence of cyclase-associated protein 1 (CAP1) and cofilin1 in neuronal actin dynamics and growth cone function.
Schneider, Felix; Duong, Thuy-An; Metz, Isabell; Winkelmeier, Jannik; Hübner, Christian A; Endesfelder, Ulrike; Rust, Marco B.
Afiliação
  • Schneider F; Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032, Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Giessen, 35032, Marburg, Germany; DFG Research Training Group, Membrane Plasticity in Tis
  • Duong TA; Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032, Marburg, Germany.
  • Metz I; Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032, Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Giessen, 35032, Marburg, Germany.
  • Winkelmeier J; Department of Systems and Synthetic Microbiology, Max Planck Institute for Terrestrial Microbiology and LOEWE Center for Synthetic Microbiology (SYNMIKRO), 35043, Marburg, Germany; Department of Physics, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, PA, USA.
  • Hübner CA; Institute of Human Genetics, University Hospital Jena, 07743, Jena, Germany.
  • Endesfelder U; Department of Systems and Synthetic Microbiology, Max Planck Institute for Terrestrial Microbiology and LOEWE Center for Synthetic Microbiology (SYNMIKRO), 35043, Marburg, Germany; Department of Physics, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, PA, USA.
  • Rust MB; Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032, Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus-Liebig-University Giessen, 35032, Marburg, Germany; DFG Research Training Group, Membrane Plasticity in Tis
Prog Neurobiol ; 202: 102050, 2021 07.
Article em En | MEDLINE | ID: mdl-33845164
ABSTRACT
Neuron connectivity depends on growth cones that navigate axons through the developing brain. Growth cones protrude and retract actin-rich structures to sense guidance cues. These cues control local actin dynamics and steer growth cones towards attractants and away from repellents, thereby directing axon outgrowth. Hence, actin binding proteins (ABPs) moved into the focus as critical regulators of neuron connectivity. We found cyclase-associated protein 1 (CAP1), an ABP with unknown brain function, abundant in growth cones. Super-resolution microscopy and live cell imaging combined with pharmacological approaches on hippocampal neurons from gene-targeted mice revealed a crucial role for CAP1 in actin dynamics that is critical for growth cone morphology and function. Growth cone defects in CAP1 knockout (KO) neurons compromised neuron differentiation and was associated with impaired neuron connectivity in CAP1-KO brains. Mechanistically, by rescue experiments in double KO neurons lacking CAP1 and the key actin regulator cofilin1, we demonstrated that CAP1 was essential for cofilin1 function in growth cone actin dynamics and morphology and vice versa. Together, we identified CAP1 as a novel actin regulator in growth cones that was relevant for neuron connectivity, and we demonstrated functional interdependence of CAP1 and cofilin1 in neuronal actin dynamics and growth cone function.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Actinas / Cones de Crescimento Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Prog Neurobiol Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Actinas / Cones de Crescimento Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Prog Neurobiol Ano de publicação: 2021 Tipo de documento: Article