Molecular dissection of TNFR-TNFα bidirectional signaling reveals both cooperative and antagonistic interactions with p75 neurotrophic factor receptor in axon patterning

Publication date: Available online 28 January 2020Source: Molecular and Cellular NeuroscienceAuthor(s): K.D. Kuhn, K. Edamura, N. Bhatia, I. Cheng, S.A. Clark, C.V. Haynes, D.L. Heffner, F. Kabir, J. Velasquez, A.J. Spano, C.D. Deppmann, A.B. KeelerAbstractDuring neural development, complex organisms rely on progressive and regressive events whereby axons, synapses, and neurons are overproduced followed by selective elimination of a portion of these components. Tumor necrosis factor α (TNFα) together with its cognate receptor (Tumor necrosis factor receptor 1; TNFR1) have been shown to play both regressive (i.e. forward signaling from the receptor) and progressive (i.e. reverse signaling from the ligand) roles in sympathetic neuron development. In contrast, a paralog of TNFR1, p75 neurotrophic factor receptor (p75NTR) promotes mainly regressive developmental events in sympathetic neurons. Here we examine the interplay between these paralogous receptors in the regulation of axon branch elimination and arborization. We confirm previous reports that these TNFR1 family members are individually capable of promoting ligand-dependent suppression of axon growth and branching. Remarkably, p75NTR and TNFR1 physically interact and p75NTR requires TNFR1 for ligand-dependent axon suppression of axon branching but not vice versa. We also find that p75NTR forward signaling and TNFα reverse signaling are functionally antagonistic. Finally, we find that TNFα reverse signaling is necessary...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research