RT Journal Article
SR Electronic
T1 TRAF6 controls spinogenesis instructing synapse density and neuronal activity through binding neuroplastin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 768341
DO 10.1101/768341
A1 Sampath Kumar Vemula
A1 Ayse Malci
A1 Lennart Junge
A1 Anne-Christin Lehmann
A1 Ramya Rama
A1 Johannes Hradsky
A1 Ricardo A. Matute
A1 André Weber
A1 Matthias Prigge
A1 Michael Naumann
A1 Michael R. Kreutz
A1 Constanze I. Seidenbecher
A1 Eckart D. Gundelfinger
A1 Rodrigo Herrera-Molina
YR 2020
UL http://biorxiv.org/content/early/2020/03/18/768341.abstract
AB Synaptogenic mechanisms and their relevance to achieve a correct synapse density and activity in mature neurons are poorly understood. Here, we show that the tumor necrosis factor receptor-associated factor 6 (TRAF6) controls early spinogenesis by binding the cell adhesion molecule neuroplastin which is has been related to synapse formation in vivo. TRAF6-neuroplastin co-precipitations from brain samples and co-transfected HEK cells is explained by direct interaction of the proteins based on three-dimensional modelling and biochemical identification of intracellular amino acids of neuroplastin binding the TRAF-C domain of TRAF6 with micromolar affinity. TRAF6 was not only required for normal spinogenesis but also was strictly necessary to restore failed spinogenesis in neuroplastin-deficient neurons. Independently from neuroplastin’s extracellular adhesive properties or interaction with another known partner i.e. the plasma membrane Ca2+ ATPases, TRAF6 mediated formation of new postsynapses by neuroplastin overexpression in rat hippocampal neurons. Furthermore, TRAF6-controlled spinogenesis was required for the establishment of a correct synapse density as well as proper synaptic activity and intrinsic neuronal activity as demonstrated with intracellular and extracellular electrophysiological recordings. These findings provide a novel mechanism for early synapse formation that shapes connectivity and functioning of hippocampal neurons.