Author:
Maibach Martina A.,Piovesana Ester,Kaiser Julia,Holm Mea M.,Risic Zorica,Maurer Michael,Schwab Martin E.
Abstract
AbstractNogo-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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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