The Interaction of TRAF6 With Neuroplastin Promotes Spinogenesis During Early Neuronal Development
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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, André; Prigge, Matthias; Naumann, Michael; Kreutz, Michael R; Seidenbecher, Constanze I; Gundelfinger, Eckart D; Herrera-Molina, Rodrigo.
In: FRONT CELL DEV BIOL, Vol. 8, 09.12.2020, p. 579513.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The Interaction of TRAF6 With Neuroplastin Promotes Spinogenesis During Early Neuronal Development
AU - Vemula, Sampath Kumar
AU - Malci, Ayse
AU - Junge, Lennart
AU - Lehmann, Anne-Christin
AU - Rama, Ramya
AU - Hradsky, Johannes
AU - Matute, Ricardo A
AU - Weber, André
AU - Prigge, Matthias
AU - Naumann, Michael
AU - Kreutz, Michael R
AU - Seidenbecher, Constanze I
AU - Gundelfinger, Eckart D
AU - Herrera-Molina, Rodrigo
N1 - Copyright © 2020 Vemula, Malci, Junge, Lehmann, Rama, Hradsky, Matute, Weber, Prigge, Naumann, Kreutz, Seidenbecher, Gundelfinger and Herrera-Molina.
PY - 2020/12/9
Y1 - 2020/12/9
N2 - 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 Kd 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.
AB - 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 Kd 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.
U2 - 10.3389/fcell.2020.579513
DO - 10.3389/fcell.2020.579513
M3 - SCORING: Journal article
C2 - 33363141
VL - 8
SP - 579513
JO - FRONT CELL DEV BIOL
JF - FRONT CELL DEV BIOL
SN - 2296-634X
ER -