Article

p75NTR--live or let die.

Department of Medical Biochemistry, Ole Worms Allé Building. 170, Aarhus University, DK-8000C Aarhus, Denmark.
Current Opinion in Neurobiology (Impact Factor: 6.77). 03/2005; 15(1):49-57. DOI: 10.1016/j.conb.2005.01.004
Source: PubMed

ABSTRACT During neuronal development, neurotrophins are essential factors that promote survival, differentiation and myelination of neurons. The trophic signals are relayed to the cells via binding to Trk receptor tyrosine kinases and the p75 neurotrophin receptor. Paradoxically, the p75 neurotrophin receptor also ensures rapid and appropriate apoptosis of neonatal neurons not reaching their proper targets and transmits death signals to injured neurons. Until recently, the mechanisms by which the p75 neurotrophin receptor governs these opposing functions have remained elusive. By the identification of new ligands and cytosolic interacting partners, receptor cleavage products and coreceptors, some of these mechanisms are now being unraveled. Here, we review recent progress in delineating the molecular networks that enable p75(NTR) to dictate life and death.

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    • "These results suggest that BDNF-TrkB signaling recruits and activates the positive regulators of neurite outgrowth Cdc42 and Rac1. BDNF and its protein precursor proBDNF bind to the non-specific neurotrophin receptor p75 (p75NTR), which has been shown to negatively impact cell survival and neurite outgrowth (Nykjaer et al., 2005; Blochl and Blochl, 2007). Interestingly, proBDNF-p75NTR signaling promotes growth cone collapse via downstream activation of RhoA (Sun et al., 2012). "
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    • "This application has also been highlighted in earlier studies (Lacasa et al., 2005; Nouaille et al., 2006). The p75NTR, a C-terminally truncated, non-signaling Trk receptor modulator (Segal, 2003; Makkerh et al., 2005) is involved in the regulation of multiple neuronal activities, e.g., development of neurodevelopmental processes (Nykjaer et al., 2005), neuronal migration (Johnston et al., 2007; Snapyan et al., 2009), and also neuronal growth inhibition (Yamashita et al., 1999; von Schack et al., 2001). Physically p75NTR can potentiate Trk signaling by potentiating neurotrophin ligand binding to TrkA receptors (Barker and Shooter, 1994; Hantzopoulos et al., 1994) thus enhancing cellular neurotrophin sensitivity (Yamashita et al., 1999; von Schack et al., 2001; Ito et al., 2003). "
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    • "Upon binding, the Trk receptors evoke the survival pathways, while p75NTR is a distant member of the TNFR family and promotes apoptosis via the mitochondrial pathway (Dhanasekaran and Reddy, 2008). However, p75NTR can also promote cell survival through nuclear factor kappa B (Nykjaer et al., 2005). "
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