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

Vemula, Sampath Kumar; Malci, Ayse; Junge, Lennart; Lehmann, Anne-Christin; Rama, Ramya; Hradsky, Johannes; Matute, Ricardo A.; Weber, Andre; Prigge, Matthias; Naumann, Michael; Kreutz, Michael R.; Seidenbecher, Constanze I.; Gundelfinger, Eckart D.; Herrera-Molina, Rodrigo

Abstract

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 mu M. 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.

Más información

Título según WOS: The Interaction of TRAF6 With Neuroplastin Promotes Spinogenesis During Early Neuronal Development
Título de la Revista: Frontiers in Cell and Developmental Biology
Volumen: 8
Editorial: Frontiers
Fecha de publicación: 2020
DOI:

10.3389/fcell.2020.579513

Notas: ISI