The lonely dance of a receptor: a new model to explain the life and the death of neurons

 

Laura Marchetti and the group Bio@SNS published a paper who deals with the behaviour of neurotrophns receptor p75 on PNAS . The p75 neurotrophin (NT)  receptor (p75NTR) plays a crucial role in balancing survival-versus-death decisions in the nervous system. Yet, despite 2 decades of structural and biochemical studies, a comprehensive, accepted model for p75NTR activation by NT ligands is still missing. Here, we present a single-molecule study of  membrane p75NTR in living cells, demonstrating that the vast majority of receptors are monomers before and after NT activation. Interestingly, the stoichiometry and diffusion properties of the wild-type (wt) p75NTR are almost identical to those of a receptor mutant lacking residues previously believed to induce oligomerization. The wt p75NTR and mutated (mut) p75NTR differ in their partitioning in cholesterol-rich membrane regions upon nerve growth factor (NGF) stimulation: the autohors argue that this is the origin of the ability of wt p75NTR , but not of mut p75NTR, to mediate immature NT (proNT)-induced apoptosis. Both p75NTR forms support proNT-induced growth cone retraction: it has been shown that receptor surface accumulation is the driving force for cone  collapse. Overall, the data unveil the multifaceted activity of the p75NTR monomer and let the authors provide a coherent interpretative frame of existing conflicting data in the literature.

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