Ternary complex with Trk, p75, and an ankyrin-rich membrane spanning protein

Neurotrophins play many critical roles in regulating neuronal plasticity, survival, and differentiation in the nervous system. Neurotrophins recognize two different receptors, the Trk receptor tyrosine kinase and the p75 neurotrophin receptor, which are associated closely. Several adaptor proteins are associated with each receptor. An ankyrin-rich membrane spanning protein (ARMS), originally identified as a substrate for protein kinase D (Kidins220) and as a p75 interacting protein, serves as a novel downstream target of Trk receptor tyrosine kinases. Kidins220/ARMS is co-expressed frequently with Trk and p75 and represents the only membrane-associated protein known to interact with both receptors. We report here that a ternary complex can be formed between Trk, p75, and Kidins220/ARMS. The extracellular domains of the TrkA and the p75 receptors are necessary for their association, whereas the juxtamembrane region of p75 was responsible for the interaction with Kidins220/ARMS. Interestingly, increasing the level of Kidins220/ARMS expression resulted in a decreased association of TrkA with p75. These findings thus suggest that Kidins220/ARMS plays an important role in regulating interactions between Trk and p75 neurotrophin receptors.