ABSTRACT
Neurotrophic factors play important roles in the normal development, maintenance and repair of the nervous system (review: Lewin & Barde, 1996). One family of neurotrophic factors, the neurotrophins, has been described from their relationship with the well characterised nerve growth factor (NGF). The neurotrophins can bind specifically to two types of cell surface protein: the trk family of transmembrane receptor tyrosine kinases (Barbacid, 1995) and p75, the low affinity neurotrophin receptor (Chao & Hempstead, 1995). The high affinity neurotrophin receptors (trkA, trkB and trkC) mediate the biological effects of neurotrophins in responsive neurons; however, the function of the p75 receptor is less clear. Studies with some null p75 mice suggest p75 is not essential for mediating the action of neurotrophins on neurons, but these studies are not conclusive. Accumulating evidence has shown that p75 may have functional roles including mediating the binding of NGF to the trkA receptor and directly or indirectly promoting apoptosis. The observation that Schwann cells dramatically upregulate their expression of p75 after axotomy led to the hypothesis that p75 played an important and perhaps critical role in peripheral nerve regeneration (Johnson, 1988). Although initial studies using null p75 mice indicated that this was not the case, more recent studies support the notion that p75 is involved in facilitating the directional growth of neurotrophin responsive neurons in association with glia expressing high levels of p75. This selective overview of the p75 literature focused on the roles of p75 particularly after nerve injury, but also includes a brief outline of its properties and diverse functions to aid the non-specialist reader. This approach also seems appropriate to help appreciate the many changes in focus which have resulted from each new wave of research into this enigmatic molecule. Readers are referred to a number of excellent reviews for specific details of neurotrophins, trks and p75 (details below).
