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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    ABSTRACT: Adult neurogenesis, restricted to specific regions in the mammalian brain, represents one of the most interesting forms of plasticity in the mature nervous system. Adult-born hippocampal neurons play important roles in certain forms of learning and memory, and altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases such as major depression and epilepsy. Newborn neurons go through distinct developmental steps, from a dividing neurogenic precursor to a synaptically integrated mature neuron. Previous studies have uncovered several molecular signaling pathways involved in distinct steps of this maturational process. In this context, the small Rho GTPases, Cdc42, Rac1, and RhoA have recently been shown to regulate the morphological and synaptic maturation of adult-born dentate granule cells in vivo. Distinct upstream regulators, including growth factors that modulate maturation and integration of newborn neurons have been shown to also recruit the small Rho GTPases. Here we review recent findings and highlight the possibility that small Rho GTPases may act as central assimilators, downstream of critical input onto adult-born hippocampal neurons contributing to their maturation and integration into the existing dentate gyrus (DG) circuitry.
    Frontiers in Synaptic Neuroscience 08/2013; 5:4. DOI:10.3389/fnsyn.2013.00004
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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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    ABSTRACT: Bioluminescence resonance energy transfer (BRET) is an improved version of earlier resonance energy transfer technologies used for the analysis of biomolecular protein interaction. BRET analysis can be applied to many transmembrane receptor classes, however the majority of the early published literature on BRET has focused on G protein-coupled receptor (GPCR) research. In contrast, there is limited scientific literature using BRET to investigate receptor tyrosine kinase (RTK) activity. This limited investigation is surprising as RTKs often employ dimerization as a key factor in their activation, as well as being important therapeutic targets in medicine, especially in the cases of cancer, diabetes, neurodegenerative, and respiratory conditions. In this review, we consider an array of studies pertinent to RTKs and other non-GPCR receptor protein-protein signaling interactions; more specifically we discuss receptor-protein interactions involved in the transmission of signaling communication. We have provided an overview of functional BRET studies associated with the RTK superfamily involving: neurotrophic receptors [e.g., tropomyosin-related kinase (Trk) and p75 neurotrophin receptor (p75NTR)]; insulinotropic receptors [e.g., insulin receptor (IR) and insulin-like growth factor receptor (IGFR)] and growth factor receptors [e.g., ErbB receptors including the EGFR, the fibroblast growth factor receptor (FGFR), the vascular endothelial growth factor receptor (VEGFR) and the c-kit and platelet-derived growth factor receptor (PDGFR)]. In addition, we review BRET-mediated studies of other tyrosine kinase-associated receptors including cytokine receptors, i.e., leptin receptor (OB-R) and the growth hormone receptor (GHR). It is clear even from the relatively sparse experimental RTK BRET evidence that there is tremendous potential for this technological application for the functional investigation of RTK biology.
    Frontiers in Endocrinology 04/2013; 4:46. DOI:10.3389/fendo.2013.00046
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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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    ABSTRACT: Glaucoma is a disease in which retinal ganglion cells (RGCs) die leading ultimately to blindness. Over the past decade and a half, information has begun to emerge regarding specific molecular responses of the retina to conditions of elevated intraocular pressure (IOP). It is now clear that the state of the RGC in glaucoma depends on a balance of pro-survival and pro-death pathways in the retina and details of these responses are still being worked out. In this review, we will discuss the evidence supporting the involvement of specific apoptotic cascades as well as the insults that trigger RGC apoptosis. In addition, we will present evidence supporting the existence of endogenous protective mechanisms as well as exogenous neuroprotective strategies.
    Experimental Eye Research 07/2010; 91(1):48-53. DOI:10.1016/j.exer.2010.04.002 · 3.02 Impact Factor
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