The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.

Ross, Alonzo H.; Daou, Marie‐Claire; McKinnon, Christine A.; Condon, Peter J.; Lachyankar, Mahesh B.; Stephens, Robert M.; Kaplan, David R.; Wolf, David E.

doi:10.1083/jcb.132.5.945

Cited by 69 publications

(44 citation statements)

References 52 publications

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“…10 recent evidence in TrkB.T1 induces dendritic filopodia via p75 NTR fact indicates a ligand-independent molecular interaction of both TrkB.FL and intracellularly truncated TrkB.FL (resembling TrkB.T1) with the p75 NTR receptor in HEK A293 cells, and also shows a role of these heteromeric receptor complexes in ligand discrimination (Bibel et al, 1999). Similar results have been described with respect to a molecular interaction of TrkA with p75 NTR (Ross et al, 1996;Gargano et al, 1997) and a functional interaction of TrkC receptors with p75 NTR (Hapner et al, 1998) in non-neuronal cells. Our data now provide the first evidence for a possible physiological function of a TrkB-p75 NTR heteromeric receptor in neurons (see above).…”

Section: Trkbt1-induced Morphological Changessupporting

confidence: 73%

Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor

Hartmann

Brigadski

Erdmann

et al. 2004

Journal of Cell Science

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The Trk family of receptor tyrosine kinases and the p75 receptor (p75NTR) mediate the effects of neurotrophins on neuronal survival, differentiation and synaptic plasticity. The neurotrophin BDNF and its cognate receptor tyrosine kinase, TrkB.FL, are highly expressed in neurons of the central nervous system. At later stages in postnatal development the truncated TrkB splice variants (TrkB.T1, TrkB.T2) become abundant. However, the signalling and function of these truncated receptors remained largely elusive. We show that overexpression of TrkB.T1 in hippocampal neurons induces the formation of dendritic filopodia, which are known precursors of synaptic spines. The induction of filopodia by TrkB.T1 occurs independently of neurotrophin binding and of kinase activity of endogenous TrkB.FL. Coexpression of a p75NTR lacking an intracellular domain inhibits the TrkB.T1-induced effect in a dominant negative manner. Steric hindrance of extracellular p75NTR interactions with a specific antibody, or absence of p75NTR with an intact extracellular domain also inhibit this TrkB.T1-induced effect. We thus propose a novel signalling pathway initiated by neurotrophin-independent extracellular or intramembrane interaction of TrkB.T1 with the p75NTR receptor, which modulates dendritic growth via p75NTR signalling cascades.

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Section: Trkbt1-induced Morphological Changessupporting

confidence: 73%

Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor

Hartmann

Brigadski

Erdmann

et al. 2004

Journal of Cell Science

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“…Since all the mutant versions of the NGF receptors utilized in this work preserve the transmembrane region, it can be argued that extensive contacts in the intra-or in the extracellular domains are necessary to stabilize the possibly weak interaction of the transmembrane domains. NGF does not modulate the interaction between TrkA and p75 either in the present study or in a previous one (Ross et al, 1996). It is therefore possible that their reciprocal affinity for binding is a property not subjected to regulation; nevertheless, other explanations may hold true.…”

Section: Discussioncontrasting

confidence: 61%

“…It should be noted that recently other authors have demonstrated a direct interaction between p75 and TrkA in the same cell system by using a copatching technique (Wolf et al, 1995;Ross et al, 1996). They have also argued that the ectodomains of p75 and TrkA proteins are responsible for reciprocal interaction, although a small contribution by the intracellular and transmembrane domains was detected (Ross et al, 1996).…”

Section: Discussionmentioning

confidence: 93%

“…They have also argued that the ectodomains of p75 and TrkA proteins are responsible for reciprocal interaction, although a small contribution by the intracellular and transmembrane domains was detected (Ross et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…A direct interaction between the two NGF receptors has been demonstrated to occur in brain tissue by cross-linking studies (Huber and Chao, 1995). Indirect proof for this interaction has been recently gained by a copatching technique in non-neuronal cells ectopically expressing both receptors (Wolf et al, 1995;Ross et al, 1996). In order to gain insight into this issue, we have coexpressed the two NGF receptors and some derived mutants lacking either the intracellular or the extracellular domains in insect cells (Sf9).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors

1997

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While the central role played by TrkA in nerve growth factor (NGF) signalling has been established by dissecting its signal transduction pathways, insight into the mechanism of action of p75LNR, the low-affinity neurotrophin receptor, has only recently been achieved. The relative contribution of p75LNR and TrkA to the constitution of high-affinity receptors for NGF and, similarly, with TrkB an TrkC to the formation of those for other neurotrophins, is presently under debate. Some form of collaboration in mediating neurotrophin activities has been observed between the Trk and p75LNR receptors, but only recent indirect evidence indicates a molecular interaction. In the present work, we have ectopically coexpressed p75LNR and TrkA in Sf9 insect cells by using baculovirus vectors, and show a direct association between the two NGF receptors. In addition, we show that the intracellular and extracellular domains of both receptors contribute to this interaction. Finally, we demonstrate that NGF becomes endocytosed in TrkA-expressing cells but not in p75LNR-expressing cells, and that such function can be modulated by the presence of the intracellular domain of p75LNR receptor.

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Neuronal differentiation in human neuroblastoma cells by nerve growth factor following TrkA up-regulation by interferon-?

Shikata

Sotozono

et al. 2000

Med. Pediatr. Oncol.

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Background TrkA mRNA expression has been reported to be related to favorable outcome of neuroblastoma (NB). Previously, we found that interferon‐γ (IFN‐γ) can enhance TrkA mRNA expression in NB cell lines. In the present study, we examined the effect of nerve growth factor (NGF) on IFN‐γ‐induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB. Procedure The effect of IFN‐γ on the TrkA mRNA expression was screened in six human NB cell lines and a freshly prepared sample, SK‐rib, from a stage IV patient. Using two of them, we examined their morphological change during simultaneous loading of NGF and IFN‐γ. Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti‐gp140trkA antibody and antiphospho tyrosine antibody. Results After a 4‐day treatment with 500 IU/ml IFN‐γ, TrkA mRNA increased in five cell lines and SK‐rib cells in association with growth inhibition. Although the degree of morphological differentiation did not increase in proportion to the TrkA expression induced by IFN‐γ, continuous loading of both IFN‐γ and NGF caused marked morphological differentiation in a cultured KP‐N‐RT cell line and SK‐rib cells during 10 days. Moreover, 5 min of NGF stimulation after IFN‐γ treatment caused the phosphorylation of TrkA protein and downstream proteins. Conclusions IFN‐γ could induce the functional NGF receptor even in the aggressive phenotype of NB. Med. Pediatr. Oncol. 34:394–401, 2000. © 2000 Wiley‐Liss, Inc.

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The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.

Cited by 69 publications

References 52 publications

Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor

Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor

Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors

Neuronal differentiation in human neuroblastoma cells by nerve growth factor following TrkA up-regulation by interferon-?

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