to activate other second messengers is conserved. The p75ECD-binding interface to NT-3 can be divided into three main contact sites, two in the case of NGF, that are stabilized by hydrophobic interactions, salt bridges, and hydrogen bonds. The junction regions between CDR1 and CDR2 form the site 1 that contains five hydrogen bonds and one salt bridge. Site 2 is formed by equal contributions from CDR3 and CRD4 and involves two salt bridges and two hydrogen bonds. Site 3, in the CRD4, includes only one salt bridge. Function Interactions with neurotrophins Neurotrophins that interact with p75NTR include NGF, NT-3, BDNF, and NT-4/5. Neurotrophins activating p75NTR may initiate apoptosis (for example, via c-Jun N-terminal kinases signaling, and subsequent p53, Jax-like proteins and caspase activation). This effect can be counteracted by anti-apoptotic signaling by TrkA. Neurotrophin binding to p75NTR, in addition to apoptotic signaling, can also promote neuronal survival (for example, via NF-kB activation). There are multiple targets of Akt that could play a role in mediating p75NTR-dependent survival, but one of the more intriguing possibilities is that Ant-induced phosphorylation of IkB kinase 1 (IKK1) plays a role in the induction of NF-kB. Interactions with proneurotrophins Proforms of NGF and BNDF (proNGF and proBNDF) are precursors to NGF and BNDF. proNGF and proBNDF interact with p75NTR and cause p75NTR-mediated apoptosis without activating TrkA-mediated survival mechanisms. Cleavage of proforms into mature Neurotrophins allows the mature NGF and BDNF to activate TrkA-mediated survival mechanisms. Sensory development Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons, and in repair of muscle and nerve damage in adults. Two distinct subpopulations of Olfactory ensheathing glia have been identified with high or low cell surface expression of low-affinity nerve growth factor receptor (p75). Interactions with other receptors Sortilin Sortilin is required for many apoptosis-promoting p75NTR reactions, functioning as a co-receptor for the binding of neurotrophins such as BDNF. pro-neurotrophins (such as proBDNF) bind especially well to p75NTR when sortilin is present. Crosstalk with Trk receptors When p75NTR initiates apoptosis, NGF binding to Tropomyosin receptor kinase A (TrkA) can negate p75NTR apoptotic effects. p75NTR c-Jun kinase pathway activation (which causes apoptosis) is suppressed when NGF binds to TrkA. p75NTR activation of NF-kB, which promotes survival, is unaffected by NGF binding to TrkA. Nogo-66 receptor (NgR1) p75NTR functions in a complex with Nogo-66 receptor (NgR1) to mediate RhoA-dependent inhibition