The p75 NGF Receptor Exposed

摘要

Among growth factors, the NGF (nerve growth factor) family of neurotrophins has always behaved in unorthodox ways. First, the neurotrophins bind to two completely different cell surface receptors―the Trk tyrosine kinase receptors (TrkA, TrkB, and TrkC) and the shared p75 receptor (see the figure). These ligand-receptor interactions produce a dazzling array of effects, lasting from milliseconds to days, that influence neuronal cell plasticity and survival. Second, each receptor forms myriad interactions with other plasma membrane receptors. The Trk receptors interact with ion channels, such as TRPC3, the TRPV1 capsaicin receptor, and a voltage-sensitive sodium channel (2). In contrast, p75 associates with the leucine-rich repeat proteins Nogo receptor and LINGO, which are involved in axonal regeneration (3), and sortilin, a trafficking receptor that brings the precursor form of NGF (proNGF) together with p75. In addition, Trk and p75 mutually form complexes that contribute to high-affinity binding of neurotrophins. In contrast to the Trk receptors, which display a more selective preference for their lig-ands, p75 binds to all neurotrophins including brain-derived neurotrophic factor (BDNF), NT-3, and NT-4.