The Interaction of TRAF6 With Neuroplastin Promotes Spinogenesis During Early Neuronal Development.

Autor: Vemula SK; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Malci A; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Junge L; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Lehmann AC; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Rama R; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Hradsky J; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Matute RA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, United States.; Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O'Higgins, Santiago, Chile., Weber A; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Prigge M; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany., Naumann M; Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany., Kreutz MR; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Seidenbecher CI; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany., Gundelfinger ED; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.; Center for Behavioral Brain Sciences, Magdeburg, Germany.; Medical Faculty, Otto von Guericke University, Magdeburg, Germany., Herrera-Molina R; Laboratory of Synaptic Signaling, Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.; Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O'Higgins, Santiago, Chile.; Center for Behavioral Brain Sciences, Magdeburg, Germany.
Jazyk: angličtina
Zdroj: Frontiers in cell and developmental biology [Front Cell Dev Biol] 2020 Dec 09; Vol. 8, pp. 579513. Date of Electronic Publication: 2020 Dec 09 (Print Publication: 2020).
DOI: 10.3389/fcell.2020.579513
Abstrakt: Correct brain wiring depends on reliable synapse formation. Nevertheless, signaling codes promoting synaptogenesis are not fully understood. Here, we report a spinogenic mechanism that operates during neuronal development and is based on the interaction of tumor necrosis factor receptor-associated factor 6 (TRAF6) with the synaptic cell adhesion molecule neuroplastin. The interaction between these proteins was predicted in silico and verified by co-immunoprecipitation in extracts from rat brain and co-transfected HEK cells. Binding assays show physical interaction between neuroplastin's C-terminus and the TRAF-C domain of TRAF6 with a K d value of 88 μM. As the two proteins co-localize in primordial dendritic protrusions, we used young cultures of rat and mouse as well as neuroplastin-deficient mouse neurons and showed with mutagenesis, knock-down, and pharmacological blockade that TRAF6 is required by neuroplastin to promote early spinogenesis during in vitro days 6-9, but not later. Time-framed TRAF6 blockade during days 6-9 reduced mEPSC amplitude, number of postsynaptic sites, synapse density and neuronal activity as neurons mature. Our data unravel a new molecular liaison that may emerge during a specific window of the neuronal development to determine excitatory synapse density in the rodent brain.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2020 Vemula, Malci, Junge, Lehmann, Rama, Hradsky, Matute, Weber, Prigge, Naumann, Kreutz, Seidenbecher, Gundelfinger and Herrera-Molina.)
Databáze: MEDLINE
Externí odkaz: