Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Inhibit Dendritic Growth in Cultured Sympathetic Neurons

Drahushuk, Karen M.; Connell, Terry D.; Higgins, Dennis

doi:10.1523/jneurosci.22-15-06560.2002

Cited by 27 publications

(20 citation statements)

References 80 publications

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“…However, our previous report that Rit is involved in p38 activation by PACAP38 (Shi et al. 2006) coupled with evidence demonstrating that PACAP38 inhibits BMP‐induced dendritic growth in cultured sympathetic neurons (Drahushuk et al. 2002) certainly suggests this possibility.…”

Section: Discussionmentioning

confidence: 99%

“…Ligands shown to cause regressive dendritic events include corticosteroids (McEwen 2001; Joels et al. 2007), excitatory amino acids such as glutamate (Mattson 1988; Monnerie and Le Roux 2007), the neuropeptides pituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal peptide (Drahushuk et al. 2002) and proinflammatory cytokines (Guo et al.…”

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confidence: 99%

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Rit signaling contributes to interferon‐γ‐induced dendritic retraction via p38 mitogen‐activated protein kinase activation

Andres¹,

Shi²,

Bruun³

et al. 2008

Journal of Neurochemistry

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The proinflammatory cytokine interferon‐γ (IFNγ) alters neuronal connectivity via selective regressive effects on dendrites but the signaling pathways that mediate this effect are poorly understood. We recently demonstrated that signaling by Rit, a member of the Ras family of GTPases, modulates dendritic growth in primary cultures of sympathetic and hippocampal neurons. In this study, we investigated a role for Rit signaling in IFNγ‐induced dendritic retraction. Expression of a dominant negative Rit mutant inhibited IFNγ‐induced dendritic retraction in cultured embryonic rat sympathetic and hippocampal neurons. In pheochromacytoma cells and hippocampal neurons, IFNγ caused rapid Rit activation as indicated by increased GTP binding to Rit. Silencing of Rit by RNA interference suppressed IFNγ‐elicited activation of p38 MAPK in pheochromacytoma cells, and pharmacological inhibition of p38 MAPK significantly attenuated the dendrite‐inhibiting effects of IFNγ in cultured sympathetic and hippocampal neurons without altering signal transducer and activator of transcription 1 activation. These observations identify Rit as a downstream target of IFNγ and suggest that a novel IFNγ‐Rit‐p38 signaling pathway contributes to dendritic retraction and may, therefore, represent a potential therapeutic target in diseases with a significant neuroinflammatory component.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Rit signaling contributes to interferon‐γ‐induced dendritic retraction via p38 mitogen‐activated protein kinase activation

Andres¹,

Shi²,

Bruun³

et al. 2008

Journal of Neurochemistry

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“…Moreover, there is evidence for interactions between these two classes of stimulatory molecules, with sympathetic neurons requiring simultaneous exposure to both a member of the BMP family and to nerve growth factor (NGF) for optimal dendritic growth (Lein et al, 1995). A variety of cytokines and hormones have also been found to inhibit dendritic growth (Guo et al, 1999;Chandrasekaran et al, 2000;Drahushuk et al, 2002;Kim et al, 2002). However, the signaling cascades triggered by these stimulatory and inhibitory agents and their interactions remain poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons

et al. 2004

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NGF activates several signaling cascades in sympathetic neurons. We examined how activation of one of these cascades, the ERK/MAP (extracellular signal-regulated kinase/mitogen-activated protein) kinase pathway, affects dendritic growth in these cells. Dendritic growth was induced by exposure to NGF and BMP-7 (bone morphogenetic protein-7). Exposure to NGF increased phosphorylation of ERK1/2. Unexpectedly, two MEK (MAP kinase kinase) inhibitors (PD 98059 and U 0126) enhanced dendritic growth, and a ligand, basic FGF, that activates the ERK pathway inhibited the growth of these processes. The enhancement of dendritic growth by PD 98059 was associated with an increase in the number of axo-dendritic synapses, and it appeared to represent a specific morphogenic effect because neither axonal growth nor cell survival was affected. In addition, increased dendritic growth was not observed after exposure to inhibitors of other signaling pathways, including the phosphatidylinositol-3-kinase inhibitor LY 294002. Dendritic growth was also increased in cells transfected with dominant-negative mutants of MEK1 and ERK2 but not with dominant-negative mutants of MEK5 and ERK5, suggesting that ERK1/2 is the primary mediator of this effect. Exposure to BMP-7 induces nuclear translocation of Smad1 (Sma-and Mad-related protein 1), and PD 98059 treatment potentiated nuclear accumulation of Smad-1 induced by BMP-7 in sympathetic neurons, suggesting a direct enhancement of BMP signaling in cells treated with an MEK inhibitor. These observations indicate that one of the signaling cascades activated by NGF can act in an antagonistic manner in sympathetic neurons and reduce the dendritic growth induced by other NGF-sensitive pathways.

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“…Among these many factors, PACAP38 has been shown to have particularly prominent and widespread effects within the nervous system (25,73,77). For example, PACAP38 treatment increases cell survival and neurite elongation in both primary neurons (21,49) and PC12 cells (13,63) and regulates dendritic growth in cultured sympathetic neurons (15). Recent studies have demonstrated a role for Rin 10).…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide 38-Mediated Rin Activation Requires Src and Contributes to the Regulation of Hsp27 Signaling during Neuronal Differentiation

Shi

Jin

Andres

2008

Molecular and Cellular Biology

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Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neuropeptide that acts through G-protein-coupled receptors. While it is well established that PACAP mediates both neurotrophic and neurodevelopmental effects, the signaling cascades that underlie these diverse actions remain incompletely characterized. Here we show that the Ras-related Rin GTP-binding protein, a GTPase that is expressed predominantly in neurons, is regulated by PACAP38 signaling, and loss-of-function analysis demonstrates that Rin makes an essential contribution to PACAP38-mediated pheochromocytoma cell differentiation. Rin is activated following stimulation of both Gs␣ and Gi␣ cascades but does not rely upon cyclic AMP (cAMP)-, Ca 2؉ -, or Epac-dependent signaling pathways. Instead, Rin is activated in a Src kinase-dependent manner. Surprisingly, Rin knockdown significantly inhibits PACAP38-mediated neurite outgrowth, without affecting mitogen-activated protein kinase signaling cascades. Instead, Rin loss attenuates PACAP38-mediated HSP27 activation by disrupting a cAMP-protein kinase A cascade. RNA interference-mediated HSP27 silencing suppresses both PACAP38-and Rin-mediated neurite outgrowth, while expression of a constitutively active Rin mutant increases both HSP27 protein and phospho-HSP27 levels, supporting a role for Rin-HSP27 signaling in neuronal differentiation. Together, these observations identify an unsuspected role for Rin in neuronal PACAP signaling and establish a novel G␣-Src-Rin-HSP27 signal transduction pathway as a critical element in PACAP38-mediated neuronal differentiation signaling.

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Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Inhibit Dendritic Growth in Cultured Sympathetic Neurons

Cited by 27 publications

References 80 publications

Rit signaling contributes to interferon‐γ‐induced dendritic retraction via p38 mitogen‐activated protein kinase activation

Rit signaling contributes to interferon‐γ‐induced dendritic retraction via p38 mitogen‐activated protein kinase activation

Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons

Pituitary Adenylate Cyclase-Activating Polypeptide 38-Mediated Rin Activation Requires Src and Contributes to the Regulation of Hsp27 Signaling during Neuronal Differentiation

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