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bioRxiv · 10.1101/2020.07.10.197368

Nogo-A Beyond the RhoA/ROCK Pathway - Novel Components of Intracellular Nogo-A Signaling Cascades

Martina A. Maibach·Ester Piovesana·Julia Kaiser·Mea M. Holm·Zorica Ristic·Michael Maurer·Martina E. Schwab
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Abstract

Nogo-A is a well-characterized myelin-associated membrane protein that restricts fibre growth and the regenerative capacity of the adult central nervous system after injury. To date Nogo-A post-receptor signalling pathway research focused on the RhoA/ROCK cascade, which can lead to growth cone collapse and neurite retraction. Much less is known about continued intracellular Nogo-A signalling mediating long-term neurite outgrowth inhibition resulting from transcriptional and translational changes. Here, we propose a simple but highly reproducible in vitro assay to study Nogo-A related signaling and neurite outgrowth inhibition in general. Furthermore, we identified ERK1/2 as downstream effector of Nogo-A, partially mediating its neurite outgrowth inhibition. We describe ERK1/2 dependent changes of translational events such as elevation of RhoA levels within the growth cone, which may potentiate the cells responses to Nogo-A. We also observed Nogo-A dependent upregulation of the JAK/STAT pathway inhibitors SOCS3 and KLF4 and downregulation of insulin mediated phosphorylation of AKT, indicating direct negative crosstalk between Nogo-A signalling and the growth promoting JAK/STAT and AKT/mTORC1 pathways.

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Martina A. Maibach, Ester Piovesana, Julia Kaiser, Mea M. Holm, Zorica Ristic, Michael Maurer, Martina E. Schwab. 2020-07-11. Nogo-A Beyond the RhoA/ROCK Pathway - Novel Components of Intracellular Nogo-A Signaling Cascades. https://doi.org/10.1101/2020.07.10.197368

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