Delta1 family members are involved in filopodial actin formation and neuronal cell migration independent of Notch signaling

Sugiyama, Kazuya; Nishide, Kenji; Matsuo, Hideaki; Okigawa, Sayumi; Okano, Makoto; Ishitani, Tohru; Matsumoto, Kunihiro; Itoh, Motoyuki

doi:10.1016/j.bbrc.2010.06.047

Cited by 2 publications

(4 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These filopodia are also modulated in N2a cells by several proteins such as Delta 1 (Sugiyama et al . ), the G protein‐coupled receptor kinase 5 (GRK5), and the actin cross‐linking family protein 7 (ACF7) (Sanchez‐Soriano et al . ).…”

Section: Resultsmentioning

confidence: 99%

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

Llorens

Carulla

Villa³

et al. 2013

Journal of Neurochemistry

View full text Add to dashboard Cite

The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP SC ) has been studied in depth, the physiological role of PrP C remains elusive and controversial.PrP C is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP C in animals and in cellular models. In this article, we present PrP C -dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP C overexpression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP C silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP C in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP C in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP C overexpression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway.

show abstract

Section: Resultsmentioning

confidence: 99%

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

Llorens

Carulla

Villa³

et al. 2013

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“… 15 , 19 , 20 , 28 , 50 Indeed, the intracellular portion of the ligand appears to modulate cell fate in cancer cells or even in cells committed to the neurogenic lineage during development. 19 , 21 – 24 Nevertheless, the mechanism by which Notch ligands influence gene transcription remains poorly understood. Notch ligand intracellular domains do not contain DNA-binding motives, suggesting that they indirectly modulate gene expression by interacting with transcription factors or other molecular co-activators.…”

Section: Discussionmentioning

confidence: 99%

“…Notch ligand intracellular domains do not contain DNA-binding motives, suggesting that they indirectly modulate gene expression by interacting with transcription factors or other molecular co-activators. 19 , 21 – 24 , 51 Competition for the γ-secretase complex between Notch receptors and ligands during activation might also account for modulation of Notch receptor-associated pathways. 15 Interestingly, recent data showed that J1ICD as well as Dll1-ICD directly interact with NICD, and inhibit Notch signalling by promoting degradation of the NICD–RBP-Jκ complex via the ubiquitin proteasome.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Jagged1 intracellular domain-mediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart

et al. 2015

View full text Add to dashboard Cite

AimsNotch1 signalling in the heart is mainly activated via expression of Jagged1 on the surface of cardiomyocytes. Notch controls cardiomyocyte proliferation and differentiation in the developing heart and regulates cardiac remodelling in the stressed adult heart. Besides canonical Notch receptor activation in signal-receiving cells, Notch ligands can also activate Notch receptor-independent responses in signal-sending cells via release of their intracellular domain. We evaluated therefore the importance of Jagged1 (J1) intracellular domain (ICD)-mediated pathways in the postnatal heart.Methods and resultsIn cardiomyocytes, Jagged1 releases J1ICD, which then translocates into the nucleus and down-regulates Notch transcriptional activity. To study the importance of J1ICD in cardiac homeostasis, we generated transgenic mice expressing a tamoxifen-inducible form of J1ICD, specifically in cardiomyocytes. Using this model, we demonstrate that J1ICD-mediated Notch inhibition diminishes proliferation in the neonatal cardiomyocyte population and promotes maturation. In the neonatal heart, a response via Wnt and Akt pathway activation is elicited as an attempt to compensate for the deficit in cardiomyocyte number resulting from J1ICD activation. In the stressed adult heart, J1ICD activation results in a dramatic reduction of the number of Notch signalling cardiomyocytes, blunts the hypertrophic response, and reduces the number of apoptotic cardiomyocytes. Consistently, this occurs concomitantly with a significant down-regulation of the phosphorylation of the Akt effectors ribosomal S6 protein (S6) and eukaryotic initiation factor 4E binding protein1 (4EBP1) controlling protein synthesis.ConclusionsAltogether, these data demonstrate the importance of J1ICD in the modulation of physiological and pathological hypertrophy, and reveal the existence of a novel pathway regulating cardiac homeostasis.

show abstract

Delta1 family members are involved in filopodial actin formation and neuronal cell migration independent of Notch signaling

Cited by 2 publications

References 33 publications

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

Jagged1 intracellular domain-mediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart

Contact Info

Product

Resources

About

Delta1 family members are involved in filopodial actin formation and neuronal cell migration independent of Notch signaling

Cited by 2 publications

References 33 publications

PrPC regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

PrPC regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

Jagged1 intracellular domain-mediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart

Contact Info

Product

Resources

About

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells

PrP^C regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells