BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K–AKT and ERK signaling pathways

Zhou, Chun; Li, C.; Li, D.; Wang, Y.; Shao, Weiwei; You, Yiran; Peng, Jingyi; Zhang, Xinwen; Lu, Lihe; Shen, X. Y.

doi:10.1016/j.neuroscience.2013.09.045

Cited by 25 publications

(22 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The target of ARFGEF1, ARF1, promotes activation of Akt and ERK1/2 in breast cancer . In addition, ARFGEF1 promotes activation of Akt and ERK1/2 in neuronal cells . Consistent with these findings, when cells were cultured on non‐adherent polyhydroxyethylmethacrylate‐coated dishes, levels of the active form of Akt (pAkt) were reduced in ARFGEF1‐knockdown cells, as well as in miR‐27b‐transfected cells (Fig.…”

Section: Resultssupporting

confidence: 74%

MicroRNA‐27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling

et al. 2015

View full text Add to dashboard Cite

The non‐receptor tyrosine kinase c‐Src is frequently activated during progression of colon cancers. In this study, we found that among the c‐Src‐regulated microRNAs (miRNAs), miR‐27b is also repressed by activation of K‐Ras/H‐Ras. Inhibitor studies suggested that the phosphatidylinositol 3‐kinase pathway is involved in the repression of miR‐27b. MicroRNA‐27b was repressed in various colon cancer cell lines and tumor tissues. Re‐expression of miR‐27b in human colon cancer HCT116 cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified ARFGEF1 and paxillin as novel targets of miR‐27b, and found that miR‐27b‐mediated regulation of ARFGEF1 is crucial for controlling anchorage‐independent growth, and that of paxillin is important for controlling cell adhesion and invasion. Re‐expression of miR‐27b suppressed the activation of c‐Src induced by integrin‐mediated cell adhesion, suggesting that repression of miR‐27b may contribute to c‐Src activation in cancer cells. These findings show that miR‐27b functions as a tumor suppressor by controlling ARFGEF1 and the paxillin/c‐Src circuit at focal adhesions.

show abstract

Section: Resultssupporting

confidence: 74%

MicroRNA‐27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Neuronal cultures were treated with hemin (75 μM) or hemin cotreated with forskolin (10 μM), 8CPT (100 μM), BFA (10 μM), 6-Bnz-cAMP (50 μM), and H-89 (10 μM; (Holz et al, 2008; Misra et al, 2005; Suzuki et al, 2010; Vliem et al, 2008; Zhou et al, 2013). The effect of these compounds, when cotreated with hemin, on neuronal survival was measured using LDH, Calcein AM assays, and MitoTracker staining.…”

Section: Resultsmentioning

confidence: 99%

“…The effect of these compounds, when cotreated with hemin, on neuronal survival was measured using LDH, Calcein AM assays, and MitoTracker staining. These concentrations were chosen as being selective for cAMP, Epac, and PKA and (Holz et al, 2008; Murray et al, 2008; Suzuki et al, 2010; Vliem et al, 2008; Zhou et al, 2013). Dose-response studies with Epac agonist 8CPT significantly reduced hemin neurotoxicity.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective role of prostaglandin PGE2 EP2 receptor in hemin-mediated toxicity

2015

View full text Add to dashboard Cite

Heme (Fe2+ protoporphyrin IX) and hemin (Fe3+), the prosthetic group of hemoprotein, are cytotoxic due to their ability to contribute to the production of reactive oxygen species, increased intracellular calcium levels and stimulate glutamate mediated-excitotoxicity. Previous work by our group showed that blockade of the prostaglandin E2 (PGE2)-EP1 receptor reduced hemin-induced cytotoxicity in primary cortical neuronal cultures. However, the role of the prostaglandin E2 (PGE2)-EP2 receptor in hemin neurotoxicity remains unclear. Activation of the EP2 receptor in neurons results in increased cyclic AMP (cAMP) and protein kinase A signaling; therefore, we hypothesized that the activation of the EP2 receptor decreases hemin neurotoxicity. Using postnatal primary cortical neurons cultured from wildtype-control (WT) and EP2−/− mice, we investigated the role of the EP2 receptor in hemin neurotoxicity by monitoring cell survival with the Calcein-AM live-cell and lactate dehydrogenase assays. MitoTracker staining was also performed to determine how mitochondria were affected by hemin. Hemin neurotoxicity in EP2−/− neurons was 37.2 ± 17.0% greater compared to WT neurons. Of interest, cotreatment with the EP2 receptor agonist, butaprost (1 and 10 μM), significantly attenuated hemin neurotoxicity by 55.7 ± 21.1% and 60.1 ± 14.8%, respectively. To further investigate signaling mechanisms related to EP2 receptor mediating cytoprotection, neurons were cotreated with hemin and activators/inhibitors of both the cAMP-protein kinase A/exchange protein directly activated by cAMP (Epac) pathways. Forskolin, a cAMP activator, and 8-pCPT-cAMP, an Epac activator, both attenuated hemin neurotoxicity by 78.8 ± 22.2% and 58.4 ± 9.8%, respectively, as measured using the lactate dehydrogenase assay. Together, the results reveal that activation of the EP2 receptor is protective against hemin neurotoxicity in vitro and these findings suggest that neuroprotection occurs through the cAMP- Epac pathway in neuronal cultures. Therefore, activation of the EP2 receptor could be used to minimize neuronal damage following exposure to supraphysiological levels of hemin.

show abstract

“…Similarly, BIG1 has been shown to regulate neurite development in vitro [17]. BIG1 localizes to the Golgi complex, and perturbation of BIG1 with BFA affects the function of the Golgi complex [14, 18].…”

Section: Introductionmentioning

confidence: 99%

BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain

et al. 2017

View full text Add to dashboard Cite

BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR), peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL) and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1) into the dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable to cross the diencephalon–telencephalon boundary (DTB). In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 μM), and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity.

show abstract

BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K–AKT and ERK signaling pathways

Cited by 25 publications

References 34 publications

MicroRNA‐27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling

MicroRNA‐27b suppresses tumor progression by regulating ARFGEF1 and focal adhesion signaling

Neuroprotective role of prostaglandin PGE2 EP2 receptor in hemin-mediated toxicity

BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain

Contact Info

Product

Resources

About