A cell-biological model of p75NTR signaling

Neurotrophin stimulation of tropomyosin-related kinase (Trk) and p75 receptors influences cellular processes such as proliferation, growth, differentiation, and other cell-specific functions, as well as regeneration. In contrast to Trk receptors, which have a well-defined trophic role, p75 has activities ranging from trophism to apoptosis. Continued neurotrophin stimulation of differentiating neurons transforms the initially trophic character of p75 signaling into negative growth control and overstimulation leads to apoptosis. This function shift reflects the signaling effects of ceramide that is generated upon stimulation of p75. The use of ceramide signaling by p75 may provide a key to understanding the cell-biological role of p75. The review presents arguments that the control of cell shape formation and cell selection can serve as an organizing principle of p75 signaling. Concurrent stimulation by neurotrophins of p75 and Trk receptors constitutes a dual growth control with antagonistic and synergistic elements aimed at optimal morphological and functional integration of cells and cell populations into their context.