P75 neurotrophin receptors

Bronfman, F.C., Tcherpakov, M., Jovin, T.M., and Fainzilber, M. (2003) Ligand-induced internalization of the p75 neurotrophin receptor A slow route to the signaling endosome. J. Neurosci. 23(8), 3209-3220. 

Analytical flow cytometry offers a rapid and facile means of monitoring cellular receptor content. For example, multiparameter flow cytometry techniques were used to monitor expression of GABAa receptor subunits during neurogenesis in embryonic rat brain (Marie et al., 2001). The content of the cell surface p75 neurotrophin receptor was measured in a heterogeneous population of mouse dorsal root sensory neurons, from which high and low p75 subsets were subsequently isolated by cell sorting (Barrett et al., 1998). 

Barrett GL, Georgiou A, Reid K, Bartlett PF, Leung D. 1998. Rescue of dorsal root sensory neurons by nerve growth factor and neurotrophin-3, but not brain-derived neurotrophic factor or neurotrophin-4, is dependent on the level of the p75 neurotrophin receptor. Neuroscience 85 1321-1328. 

NGF acting via the p75 neutrophin receptor promotes cell death during the SC injury or infection via activation of c-jun-N-terminal kinase (JNK). It has been found that neonatal p75 neurotrophin receptor mutant mice are less prone to cell death after nerve transaction. Here it is to be noted that the same neurotrophin signaling pathway may also promote survival of... 

Neumann H, Misgeld T, Matsumuro K, Wekerle H (1998) Neuro-trophins inhibit major histocompatibility class II inducibility of microglia Involvement of the p75 neurotrophin receptor. Proc Natl Acad Sci USA 95 5779-5784. 

The neurotrophins are unusual among polypeptide growth factors in that two different transmembrane proteins serve as receptors for each neurotrophin. The structural features of Trk tyrosine kinases and the p75 neurotrophin receptor are displayed in Fig. 1. The Trk subfamily of receptor tyrosine kinases is distinguished by immunoglobulin-C2 domains and repeats rich in leucine and cysteine residues in the extracellular domain and a tyrosine kinase domain with a small interruption and a short cytoplasmic tail. 

Fig. 1. Transitiembrane receptors for NGF. Whereas the TrkA receptor is a member of tyrosine kinase family of receptor, the p75 neurotrophin receptor belongs to the TNF superfamily of receptors. A schematic representation of the TrkA and the p75 neurotrophin receptor is shown, together with their substrates and adaptor proteins Trk adaptor proteins include FRS II (Kouhara et al., 1997) and SH2B (Qian et al., 1998). Signal transduction by the neurotrophins involves recruitment of enzymatic activities, such as phosphatidylinositol 3 kinase (PI3-K) and phospholipase C--y for TrkA (Kaplan and Stephens, 1994) and TRAF6 for p75 (Khursigara et al., 1999).

Bamji, S., Majdan, M., Pozniak, C.D., Belliveau, D.J., Aloyz R, J.K., Causing, C.G., Miller, F.D., 1998. The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J. Cell Biol. 140, 911-923. 

Khursigara, G., Orlinick, J.R., Chao, M.V., 1999. Association of TRAF6 with the p75 neurotrophin receptor. J. Biol. Chem. 274, 2597-2600. 

Chu GK, Yu W, Fehlings MG (2007) The p75 neurotrophin receptor is essential for neuronal cell survival and improvement of functional recovery after spinal cord injury. Neuroscience... 

Sotthibundhu A, Sykes AM, Fox B, Underwood CK, Thangnipon W, Coulson EJ (2(X)8) Beta-amyloid(l-42) induces neurontil death through the p75 neurotrophin receptor. J Neurosci... 

Epa et al. prepared a 5 -adamantyl (hnked to the ODN by a carboxylaminohexyl group) antisense phosphorothioate-ODN against the p75 neurotrophin receptor, and proved its efficacy in the presence of 6 both in vitro and in vivo [132]. Accordingly,... 

Ligand based discovery of potent smaii moiecuies that up-regulate p75 neurotrophin receptor in vitro. 

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