Cross-talk between growth factor and purinergic signalling regulates Schwann cell proliferation

Abstract

Axons provide multiple mitogenic signals to Schwann cells (SCs), yet at an appropriate stage of development, SCs stop dividing despite the mitogenic action of axolemma and growth factors. This implies that the effect of mitogens on cell proliferation may be context-dependent, having different effects on cell proliferation depending upon other signals in the extracellular environment. Recent research has shown that the effects of adenosine on SC proliferation depend upon the growth factor environment, and that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signalling pathway is an important point of integration between purinergic and growth factor signalling. In the absence of growth factors, adenosine is mitogenic and associated with stimulation of the ERK/MAPK pathway in SCs. However, in the presence of growth factors (platelet-derived growth factor or neuregulin), adenosine has the opposite effect, inhibiting proliferation and ERK/MAPK activation. Together these findings suggest a mechanism by which increased neural impulse activity could modulate growth factor signalling to both positively and negatively regulate SC proliferation before the onset of myelination.