scholarly journals c-Fos Activated Phospholipid Synthesis Is Required for Neurite Elongation in Differentiating PC12 Cells

2004 ◽  
Vol 15 (4) ◽  
pp. 1881-1894 ◽  
Author(s):  
Germán A. Gil ◽  
Daniela F. Bussolino ◽  
Maximiliano M. Portal ◽  
Adolfo Alfonso Pecchio ◽  
Marianne L. Renner ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Dual Function ◽  
Phospholipid Synthesis ◽  
Nerve Growth ◽  
Neurite Elongation ◽  
Neurite Retraction ◽  
Fos Expression

We have previously shown that c-Fos activates phospholipid synthesis through a mechanism independent of its genomic AP-1 activity. Herein, using PC12 cells induced to differentiate by nerve growth factor, the genomic effect of c-Fos in initiating neurite outgrowth is shown as distinct from its nongenomic effect of activating phospholipid synthesis and sustaining neurite elongation. Blocking c-Fos expression inhibited differentiation, phospholipid synthesis activation, and neuritogenesis. In cells primed to grow, blocking c-Fos expression determined neurite retraction. However, transfected cells expressing c-Fos or c-Fos deletion mutants with capacity to activate phospholipid synthesis sustain neurite outgrowth and elongation in the absence of nerve growth factor. Results disclose a dual function of c-Fos: it first releases the genomic program for differentiation and then associates to the endoplasmic reticulum and activates phospholipid synthesis. Because phospholipids are key membrane components, we hypothesize this latter phenomenon as crucial to support membrane genesis demands required for cell growth and neurite elongation.

scholarly journals Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells

FEBS Letters ◽  
2010 ◽  
Vol 584 (13) ◽  
pp. 2821-2826 ◽  
Author(s):  
Toshiya Sugino ◽  
Mitsuhisa Maruyama ◽  
Masaya Tanno ◽  
Atsushi Kuno ◽  
Kiyohiro Houkin ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Nerve Growth ◽  
Protein Deacetylase

scholarly journals Different Outcomes of Unliganded and Liganded Estrogen Receptor-α on Neurite Outgrowth in PC12 Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 200-211 ◽  
Author(s):  
Yohann Mérot ◽  
François Ferrière ◽  
Luc Gailhouste ◽  
Guillaume Huet ◽  
Frédéric Percevault ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Estrogen Receptor Α ◽  
Akt Signaling ◽  
Induced Response ◽  
Nerve Growth

A precise description of the mechanisms by which estrogen receptor-α (ERα) exerts its influences on cellular growth and differentiation is still pending. Here, we report that the differentiation of PC12 cells is profoundly affected by ERα. Importantly, depending upon its binding to 17β-estradiol (17βE2), ERα is found to exert different effects on pathways involved in nerve growth factor (NGF) signaling. Indeed, upon its stable expression in PC12 cells, unliganded ERα is able to partially inhibit the neurite outgrowth induced by NGF. This process involves a repression of MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways, which leads to a negative regulation of markers of neuronal differentiation such as VGF and NFLc. This repressive action of unliganded ERα is mediated by its D domain and does not involve its transactivation and DNA-binding domains, thereby suggesting that direct transcriptional activity of ERα is not required. In contrast with this repressive action occurring in the absence of 17βE2, the expression of ERα in PC12 cells allows 17βE2 to potentiate the NGF-induced neurite outgrowth. Importantly, 17βE2 has no impact on NGF-induced activity of MAPK and Akt signaling pathways. The mechanisms engaged by liganded ERα are thus unlikely to rely on an antagonism of the inhibition mediated by the unliganded ERα. Furthermore, 17βE2 enhances NGF-induced response of VGF and NFLc neuronal markers in PC12 clones expressing ERα. This stimulatory effect of 17βE2 requires the transactivation functions of ERα and its D domain, suggesting that an estrogen-responsive element-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17βE2 in ERα-expressing PC12 cells. In the absence of its ligand, ERα partially inhibits the nerve growth factor-induced neurite outgrowth of PC12 cells, whereas, once liganded, it enhances differentiation.

scholarly journals Overexpression of HuD, but Not of Its Truncated Form HuD I+II, Promotes GAP-43 Gene Expression and Neurite Outgrowth in PC12 Cells in the Absence of Nerve Growth Factor

2002 ◽  
Vol 75 (3) ◽  
pp. 1103-1114 ◽  
Author(s):  
Kim D. Anderson ◽  
Melissa A. Morin ◽  
Andrea Beckel-Mitchener ◽  
Charlotte D. Mobarak ◽  
Rachael L. Neve ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Truncated Form ◽  
Nerve Growth

scholarly journals Adapter Protein SH2-Bβ Undergoes Nucleocytoplasmic Shuttling: Implications for Nerve Growth Factor Induction of Neuronal Differentiation

2004 ◽  
Vol 24 (9) ◽  
pp. 3633-3647 ◽  
Author(s):  
Linyi Chen ◽  
Christin Carter-Su
Keyword(s):  
Plasma Membrane ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Nuclear Export ◽  
Adapter Protein ◽  
Wild Type ◽  
Nerve Growth

ABSTRACT The adapter protein SH2-B has been shown to bind to activated nerve growth factor (NGF) receptor TrkA and has been implicated in NGF-induced neuronal differentiation and the survival of sympathetic neurons. However, the mechanism by which SH2-B enhances and maintains neurite outgrowth is unclear. We examined the ability of truncation mutants to regulate neuronal differentiation and observed that certain truncation mutants localized in the nucleus rather than in the cytoplasm or at the plasma membrane as reported for wild-type SH2-Bβ. Addition of the nuclear export inhibitor leptomycin B caused both overexpressed wild-type and endogenous SH2-Bβ to accumulate in the nucleus of both PC12 cells and COS-7 cells as did deletion of a putative nuclear export sequence (amino acids 224 to 233) or mutation of two critical lysines in that sequence. Deleting or mutating the nuclear export signal caused SH2-Bβ to lose its ability to enhance NGF-induced differentiation of PC12 cells. Neither the NGF-induced phosphorylation of ERKs 1 and 2 nor their subcellular distribution was altered in PC12 cells stably expressing the nuclear export-defective SH2-Bβ(L231A, L233A). These data provide strong evidence that SH2-Bβ shuttles constitutively between the nucleus and cytoplasm. However, SH2-Bβ needs continuous access to the cytoplasm and/or plasma membrane to participate in NGF-induced neurite outgrowth. These data also suggest that the stimulatory effect of SH2-Bβ on NGF-induced neurite outgrowth of PC12 cells is either downstream of ERKs or via some other pathway yet to be identified.

scholarly journals The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells.

1986 ◽  
Vol 102 (3) ◽  
pp. 821-829 ◽  
Author(s):  
C Richter-Landsberg ◽  
B Jastorff
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Morphological Differentiation ◽  
Intracellular Camp ◽  
Nerve Growth ◽  
Process Formation ◽  
Dependent Protein

Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differential effects on the activation of cAMP-dependent protein kinases, i.e., (Sp)-cAMPS behaves as a cAMP agonist and (Rp)-cAMPS behaves as a cAMP antagonist. Our data show that the establishment of a neuritic network, as observed from PC12 cells treated with NGF alone, could not be induced by either forskolin, cAMP, or cAMP analogues alone. The presence of NGF in combination with forskolin or cAMP or its agonistic analogues potentiated the initiation of neurite outgrowth from PC12 cells. The (Sp)-cAMPS-induced stimulation of NGF-mediated process formation was successfully blocked by the (Rp)-cAMPS diastereomer. On the other hand, NGF-stimulated neurite outgrowth was not inhibited by the presence of the cAMP antagonist (Rp)-cAMPS. We conclude that the morphological differentiation of PC12 cells stimulated by NGF does not require cAMP as a second messenger. The constant increase of intracellular cAMP, caused by either forskolin or cAMP and the analogues, in combination with NGF, not only rapidly stimulated early neurite outgrowth but also exerted a maintaining effect on the neuronal network established by NGF.

scholarly journals Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors.

1985 ◽  
Vol 101 (5) ◽  
pp. 1799-1807 ◽  
Author(s):  
D G Drubin ◽  
S C Feinstein ◽  
E M Shooter ◽  
M W Kirschner
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Time Course ◽  
Microtubule Assembly ◽  
Nerve Growth ◽  
Peripheral Neurons ◽  
Associated Proteins

Nerve growth factor (NGF) regulates the microtubule-dependent extension and maintenance of axons by some peripheral neurons. We show here that one effect of NGF is to promote microtubule assembly during neurite outgrowth in PC12 cells. Though NGF causes an increase in total tubulin levels, the formation of neurites and the assembly of microtubules follow a time course completely distinct from that of the tubulin induction. The increases in microtubule mass and neurite extension closely parallel 10- and 20-fold inductions of tau and MAP1, proteins shown previously to promote microtubule assembly in vitro. When NGF is removed from PC12 cells, neurites disappear, microtubule mass decreases, and both microtubule-associated proteins return to undifferentiated levels. These data suggest that the induction of tau and MAP1 in response to NGF promotes microtubule assembly and that these factors are therefore key regulators of neurite outgrowth.

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