Neurotrophic factor receptors: just like other growth factor and cytokine receptors?

doi:10.1016/0959-4388(94)90102-3

Current Opinion in Neurobiology

Volume 4, Issue 3, June 1994, Pages 400-405

https://doi.org/10.1016/0959-4388(94)90102-3 Get rights and content

Abstract

As the actions of neurotrophic factors appear so strikingly different from those of growth factors and cytokines operating elsewhere in the body, it was long thought that neurotrophic factors might in some way be fundamentally different from traditional growth factors and cytokines. Recent advances in the understanding of the structure of the receptors for neurotrophic factors reveals them to be much more like the receptors used by other cytokines and growth factors than was perhaps first anticipated. These findings suggest that neurotrophic factors display distinctive actions not because they utilize novel receptor systems, but rather because they activate these receptors in neurons.

References (25)

H. Thoenen
The Changing Scene of Neurotrophic Factors
Trends Neurosci
(1991)
D.J. Glass et al.
The Neurotrophins and Their Receptors
Trends Cell Biol
(1993)
S.O. Meakin et al.
The Nerve Growth Factor Family of Receptors
Trends Neurosci
(1992)
D.J. Glass et al.
Trk B Mediates BDNF/NT-3-Dependent Survival and Proliferation in Fibroblasts Lacking the Low Affinity NGF Receptor
Cell
(1991)
N.Y. Ip et al.
Similarities and Differences in the Way Neurotrophins Interact with the Trks in Neuronal and Non-Neuronal Cells
Neuron
(1993)
G. Rovelli et al.
Chimeric TNF:TrkA Receptors Reveal That Ligand-Dependent Activation of the TrkA Tyrosine Kinase is Sufficient for Differentiation and Survival of PC12 Cells
R.J. Smeyne et al.
Severe Sensory and Sympathetic Neuropathies in Mice Carrying a Disrupted Trk/NGF Receptor Gene
Nature
(1994)
N.Y. Ip et al.
Ciliary Neurotrophic Factor and its Receptor Complex
Prog Growth Factor Res
(1992)
N. Stahl et al.
The Alphas, Betas, and Kinases of Cytokine Receptor Complexes
Cell
(1993)
N.Y. Ip et al.
The α Component of the CNTF Receptor Is Required for Signaling and Defines Potential CNTF Targets in the Adult and During Development
Neuron
(1993)

N. Stahl et al.

The β Receptor Components for the CNTF/LIF/OSM/IL6 Cytokine Family Associate with and Mediate Activation of the Jak/Tyk Family of Kinases

Science

(1994)

T.G. Boulton et al.

The CNTF/LIF/IL6/ OSM Family of Cytokines Induce Tyrosine Phosphorylation of a Common Set of Proteins Overlapping those Induced by Other Cytokines and Growth Factors

J Biol Chem

(1994)

Cited by (30)

Chemokine- and neurotrophic factor-induced changes in E2F1 localization and phosphorylation of the retinoblastoma susceptibility gene product (pRb) occur by distinct mechanisms in murine cortical cultures
2005, Experimental Neurology
The retinoblastoma susceptibility gene product (pRb) and E2F1 have been found to exhibit altered localization and increased staining in several neurodegenerative diseases. We have observed similar localization in primary murine cortical cultures treated with neurotrophic factors (NTF) or chemokines. In untreated cultures, E2F1 exhibited minimal immunostaining using the KH95 antibody, which recognizes the pRb interaction domain. In primary E16 murine cortical cultures, NTF- or chemokine-treated neurons, KH95 E2F1 staining was increased in the cytoplasm. However, an antibody recognizing the amino-terminus of E2F1 (KH20) stained the cytoplasm of both untreated and treated neurons. Taken together these results suggest that the change seen in E2F1 using the KH95 antibody is due to antigen unmasking of a carboxy-terminal epitope in response to NTF and chemokines. When we assessed staining for the hyperphosphorylated, inactive form of pRb (ppRb) in untreated cultures, ppRb was predominantly cytoplasmic. In response to NTF or chemokine treatment, staining for ppRb was observed predominantly in nuclei of neurons indicating a change in subcellular distribution. Immunoblot analysis demonstrated increased levels of ppRb in response to NTF and chemokines. Inhibitors of translation, nuclear export, and phoshpatidylinositol-3-kinase blocked NTF- and chemokine-induced nuclear ppRb localization while having no effect on E2F1 staining. Instead increased cytoplasmic KH95 E2F1 staining was dependent on cytoskeletal destabilization which did not influence ppRb localization. These findings demonstrate that alterations in ppRb distribution and E2F1 antigen availability by NTF and chemokines occur by distinct mechanisms suggesting that E2F1 function may be independent of pRb regulation in post-mitotic neurons.
The expression profiles of neurotrophins and their receptors in rat and chicken tissues during development
2001, Neuroscience Letters
Neurotrophic factors are target-derived proteins that promote the survival and differentiation of the innervating neurons. Increasing evidence indicate the involvement of these factors and receptors during the formation and maturation of the neuromuscular junction. To gain further insight on the expression pattern of these factors and receptors in developing spinal cord and skeletal muscle during the critical stages of synapse formation, a systematic study was performed with chicken and rat tissues using Northern blot analysis. The expression of all the neurotrophins was detected in skeletal muscle early in development, coincidental with the appearance of their corresponding receptors in the spinal cord. Taken together, the similar regulatory patterns observed in both rat and chicken tissues suggest that the potential roles of neurotrophins at the neuromuscular synapse are conserved throughout evolution.
Response of cell cycle proteins to neurotrophic factor and chemokine stimulation in human neuroglia
2001, Experimental Neurology
Increased expression of neurotrophins (e.g., NGF, BDNF) and chemokines (e.g., RANTES) has been observed in neurodegenerative diseases. We examined the effect of these factors on intracellular signaling cascades inducing cell cycle proteins p53, pRb, and E2F1 in human fetal mixed neuronal and glial cells. Comparing neurotrophin- and chemokine-treated cultures with untreated controls showed altered subcellular localization and expression of hyperphosphorylated retinoblastoma protein (ppRb), E2F1, and p53. Using immunofluorescent laser confocal microscopy, E2F1 and ppRb were detected exclusively in neuronal nuclei in control cultures while p53 was cytoplasmic in astrocytes and nuclear in neurons. Following treatment with neurotrophins, E2F1 and ppRb were observed in the cytoplasm of neurons, while p53 was observed in both neuronal and astrocytic nuclei. Similar findings were observed following treatment with RANTES. Semiquantitative analysis using immunoblots showed an increase in the amount of phosphorylated pRb in treated cultures. Induction of cell cycle proteins may play a role in neurodegeneration associated with neurotrophin and chemokine stimulation.
Nerve growth factor potentiated the sodium butyrate- and PMA-induced megakaryocytic differentiation of K562 leukemia cells
2000, Leukemia Research
We have recently reported that retinoic acid (RA) induced the expression of trkA, the high affinity receptor for nerve growth factor (NGF), in human chronic myelogenous leukemia K562 cells. In this paper, we examined the ability of several other differentiation inducers to regulate the expression of trkA and NGF in K562 cells. We found that the expression of trkA was dramatically induced by the two megakaryocyte lineage inducers sodium butyrate (NaBut) and phorbol 12-myristate 13-acetate (PMA), but not by the two erythrocyte lineage inducers hemin or 1-β-d-arabinofuranosyl cytosine (Ara-C). Furthermore, activation of the up-regulated trkA receptor by exogenous NGF potentiated the megakaryocytic differentiation of K562 cells induced by NaBut and PMA. Our results demonstrated that trkA is one of the essential genes that are up-regulated and involved in the megakaryocytic differentiation of K562 leukemia cells triggered by these differentiation inducers. Our findings suggest that NGF, in addition to its pivotal roles in the nervous system, may also play important roles in hematopoietic differentiation.
Glial cells as targets and producers of neurotrophins
2000, International Review of Cytology
Glial cells fulfill important tasks within the neural network of the central and peripheral nervous systems. The synthesis and secretion of various polypeptidic factors (cytokines) and a number of receptors, with which glial cells are equipped, allow them to communicate with their environment. Evidence has accumulated during recent years that neurotrophins play an important role not only for neurons but also for glial cells. This brief update of some morphological, immunocytochemical, and biochemical characteristics of glial cell lineages conveys our present knowledge about glial cells as targets and producers of neurotrophins under normal and pathological conditions. The chapter discusses the presence of neurotrophin receptors on glial cells, glial cells as producers of neurotrophins, signaling pathways downstream Trk and p75NTR, and the significance of neurotrophins and their receptors for glial cells during development, in cell death and survival, and in neurological disorders.
Inducible and constitutive transcription factors in the mammalian nervous system: Control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins
1998, Brain Research Reviews
This article reviews findings up to the end of 1997 about the inducible transcription factors (ITFs) c-Jun, JunB, JunD, c-Fos, FosB, Fra-1, Fra-2, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif268); and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. In the first part we consider basic facts about the expression and activity of these transcription factors: the organization of the encoding genes and their promoters, the second messenger cascades converging on their regulatory promoter sites, the control of their transcription, the binding to dimeric partners and to specific DNA sequences, their trans-activation potential, and their posttranslational modifications. In the second part we describe the expression and possible roles of these transcription factors in neural tissue: in the quiescent brain, during pre- and postnatal development, following sensory stimulation, nerve transection (axotomy), neurodegeneration and apoptosis, hypoxia–ischemia, generalized and limbic seizures, long-term potentiation and learning, drug dependence and withdrawal, and following stimulation by neurotransmitters, hormones and neurotrophins. We also describe their expression and possible roles in glial cells. Finally, we discuss the relevance of their expression for nervous system functioning under normal and patho-physiological conditions.

View all citing articles on Scopus

View full text

Neurotrophic factor receptors: just like other growth factor and cytokine receptors?

Abstract

Trends Neurosci

Trends Cell Biol

Trends Neurosci

Cell

Neuron

Nature

Prog Growth Factor Res

Cell

Neuron

Science

J Biol Chem