Nuclear Factor-κB Activation via Tyrosine Phosphorylation of Inhibitor κB-α Is Crucial for Ciliary Neurotrophic Factor-Promoted Neurite Growth from Developing Neurons

Gallagher, Denis; Gutiérrez, Humberto; Gavaldà, Núria; O’Keeffe, Gerard W.; Hay, Ronald T.; Davies, Alun M.

doi:10.1523/jneurosci.0608-07.2007

Cited by 51 publications

(69 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with this, we found that CD3 recruitment by a CD3 antibody induced an elevation of [Ca 2ϩ ] i in cultured neurons. The expression of ZAP-70 -related tyrosine kinase in developing neurons (Ishijima et al, 1995;Yoneya et al, 1998), and the reported role of Syk in neurite outgrowth (Tsujimura et al, 2001;Gallagher et al, 2007) is compatible with the notion that Syk/ZAP-70 could be a relevant component of the intracellular transduction pathway connecting CD3 activation and Ca 2ϩ mobilization to negatively control dendritic shaping.…”

Section: Potential Mechanisms For Cd3 Neuronal Functionsupporting

confidence: 75%

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

Baudouin

Angibaud

Loussouarn

et al. 2008

MBoC

View full text Add to dashboard Cite

A novel idea is emerging that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3 is mainly expressed in neurons. Distribution of CD3 in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3 is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3 was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3 in cultured neurons or overexpression of a loss-of-function CD3 mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3 by a CD3 antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3 in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

show abstract

Section: Potential Mechanisms For Cd3 Neuronal Functionsupporting

confidence: 75%

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

Baudouin

Angibaud

Loussouarn

et al. 2008

MBoC

View full text Add to dashboard Cite

show abstract

“…Here we show for the first time that NF-B is one of the central survival pathways of embryonic spinal cord MNs. It is also known that NF-B activity is related to other neuronal functions such as neurite outgrowth (Gallagher et al, 2007;Gutierrez et al, 2008), suggesting an important role of this pathway in neuronal development and probably in some neuronal diseases (Mattson and Meffert, 2006). For example, genes regulating NF-B pathway activity have been related to a novel form of lower motor neuron disease (Maystadt et al, 2007), indicating that indirect NF-B deregulation might be involved in neuronal diseases.…”

Section: Discussionmentioning

confidence: 99%

“…However, NTFs can also activate other pathways that are crucial for the neuronal physiology. In some neuronal populations, the NF-B pathway is activated by cytokines and is responsible for cell survival and/or neurite outgrowth (Maggirwar et al, 1998;Gallagher et al, 2007). Because no information exists about the involvement of the NF-B pathway mediating MN survival, we decided to analyze this subject in our MN model.…”

Section: Neurotrophic Factor Stimulation Induces Nf-b Pathway Activatmentioning

confidence: 99%

See 1 more Smart Citation

The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

Mincheva¹,

Garcerá²,

Gou-Fàbregas³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

In vivo and in vitro motoneuron survival depends on the support of neurotrophic factors. These factors activate signaling pathways related to cell survival or inactivate proteins involved in neuronal death. In the present work, we analyzed the involvement of the nuclear factor-B (NF-B) pathway in mediating mouse spinal cord motoneuron survival promoted by neurotrophic factors. This pathway comprises ubiquitously expressed transcription factors that could be activated by two different routes: the canonical pathway, associated with IKK␣/IKK␤ kinase phosphorylation and nuclear translocation RelA (p65)/p50 transcription factors; and the noncanonical pathway, related to IKK␣ kinase homodimer phosphorylation and RelB/p52 transcription factor activation. In our system, we show that neurotrophic factors treatment induced IKK␣ and IKK␤ phosphorylation and RelA nuclear translocation, suggesting NF-B pathway activation. Protein levels of different members of the canonical or noncanonical pathways were reduced in a primary culture of isolated embryonic motoneurons using an interference RNA approach. Even in the presence of neurotrophic factors, selective reduction of IKK␣, IKK␤, or RelA proteins induced cell death. In contrast, RelB protein reduction did not have a negative effect on motoneuron survival. Together these results demonstrated that the canonical NF-B pathway mediates motoneuron survival induced by neurotrophic factors, and the noncanonical pathway is not related to this survival effect. Canonical NF-B blockade induced an increase of Bim protein level and apoptotic cell death. Bcl-x L overexpression or Bax reduction counteracted this apoptotic effect. Finally, RelA knockdown causes changes of CREB and Smn protein levels.

show abstract

“…LIGHT has multiple functions in the immune system and has been implicated in the regulation of cell proliferation and survival in several tissues and organs (Ware, 2005;Murphy et al, 2006;Pierer et al, 2007), but has no known role in the nervous system. HVEM and LT␤R lack death domains and interact with adaptors of the TRAF family to modulate several signaling pathways including the NF-B transcription family (Grivennikov et al, 2006), which has been implicated in regulating neurite growth from neonatal nodose ganglion neurons (Gutierrez et al, 2005;Gallagher et al, 2007). Here we report a novel function for LIGHT as a negative regulator of neurite growth in nodose sensory neurons by a mechanism involving the HVEM receptor and NF-B signaling inhibition.…”

Section: Introductionmentioning

confidence: 84%

Developmental Regulation of Sensory Neurite Growth by the Tumor Necrosis Factor Superfamily Member LIGHT

Gavaldà

Gutiérrez²,

Davies³

2009

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

In a PCR screen to identify novel cytokine candidates involved in neuronal development, we identified transcripts for the tumor necrosis factor superfamily member 14 (TNFSF14), generally known as LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), together with its receptors, lymphotoxin-␤ receptor (LT␤R) and TNF family receptor herpesvirus entry mediator (HVEM), in the experimentally tractable sensory neurons of the mouse nodose ganglion. Immunocytochemistry revealed coexpression of LIGHT and its receptors in all nodose ganglion neurons in neonates. Enhancing LIGHT signaling in these neurons by overexpressing LIGHT inhibited BDNF-promoted neurite growth during a narrow window of development in the immediate perinatal period without affecting neuronal survival. Overexpressing a LIGHT mutant that selectively activates HVEM, but not one that selectively activates LT␤R, also inhibited BDNF-promoted growth, suggesting that neurite growth inhibition is mediated via HVEM. Blocking HVEM signaling by a function-blocking anti-HVEM antibody significantly enhanced neurite growth from nodose neurons grown both with and without BDNF. Likewise, neurons from LIGHT-deficient neonates exhibited significantly greater neurite growth than neurons from wild-type littermates in both the presence and absence of BDNF. LIGHT overexpression significantly inhibited NF-B activity, while preventing LIGHT-induced NF-B inhibition by overexpressing the p65 and p50 NF-B subunits prevented LIGHTmediated growth inhibition. Together, these findings show that LIGHT/HVEM signaling negatively regulates neurite growth from developing sensory neurons via NF-B inhibition.

show abstract

Nuclear Factor-κB Activation via Tyrosine Phosphorylation of Inhibitor κB-α Is Crucial for Ciliary Neurotrophic Factor-Promoted Neurite Growth from Developing Neurons

Cited by 51 publications

References 26 publications

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

Developmental Regulation of Sensory Neurite Growth by the Tumor Necrosis Factor Superfamily Member LIGHT

Contact Info

Product

Resources

About