Neurotrophin receptors: Old friends with new partners

Abstract

ABSTRACT:Neurotrophins are important regulators of embryonic development and adult function of most populations of neurons in vertebrate nervous systems. This signaling system regulates many diverse activities, including survival, axon outgrowth, and synaptic plasticity. In mammals, neurotrophin action is mediated by four receptors, p75 NTR , TrkA, TrkB, and TrkC. Although early studies viewed these receptors as solitary agents in the cells outer membrane, recent discoveries reveal that the cell outer membrane is a crowded and highly interactive neighborhood. Neurotrophin receptors partner with a diverse array of membrane proteins, dramatically expanding their functional repertoire. This review will focus on some of the most recent discoveries concerning the promiscuous partnering of neurotrophin receptors. '

Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling

“…Taken together, these results indicate that BDNF/TrkB signalling activity was recapitulated by light control of optoTrkB. More importantly, they also suggest that optoTrkB expression, which, in theory, could lead to receptor auto-activation 23 , did not spontaneously cause any marked biological consequences; expression of these receptors was functionally effective only when coupled with light stimulation.…”

“…Accordingly, overexpression of them are prone to receptor auto-activation in the absence of stimulus 23 . Indeed, for example, a modest induction of optoTrkB activation in the dark state, as demonstrated by an increase in ERK phosphorylation without illumination, was evident in HeLa cells (Supplementary Figs 3a and 5a), which may limit the utility of optoTrkB.…”

p75NTR-dependent Rac1 activation requires receptor cleavage and activation of an NRAGE and NEDD9 signaling cascade

“…The p75 neurotrophin receptor (p75NTR, also known as tumor necrosis factor receptor superfamily member 16), a member of the tumor necrosis factor receptor (TNFR) superfamily, participates in an array of cellular events that include apoptosis, survival signaling, differentiation, neurite outgrowth and growth cone collapse (reviewed in Schecterson and Bothwell., 2010). Some of these are activated by the neurotrophin binding to p75NTR and, in others, p75NTR acts as an accessory receptor and signaling component for other ligand-binding receptors (reviewed in Reichardt., 2006).…”

The role of nerve growth factor and its receptors in tumorigenesis and cancer pain

“…Unlike p75NTR which can be activated by all neurotrophin family members, TrkA is activated only by particular neurotrophins (Figure 1) (40,(42)(43)(44). Like most receptor tyrosine kinases, TrkA is activated by ligand-induced formation of non-covalently associated receptor dimers (43). TrkA primarily regulates growth and differentiation of neurons in both peripheral and central nervous systems.…”