VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis

Basagiannis, Dimitris; Zografou, Sofia; Murphy, Carol; Fotsis, Theodore; Morbidelli, Lucia; Ziche, Marina; Bleck, Christopher; Mercer, Jason; Christoforidis, Savvas

doi:10.1242/dev.146456

Cited by 31 publications

(35 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the association of Dynamin 2 with inclusions that are fully internalized and the accumulation of Dynamin 2 at the neck of inclusions that are still fused to the apical membrane suggest that Dynamin 2 is involved in the internalization and excision of inclusions. Previous reports have noted that macropinocytosis is independent of Dynamin 2 (Damke et al, 1995;Saeed et al, 2010;Devadas et al, 2014;Basagiannis et al, 2016). Our data support a dynamin-dependent endocytic mechanism given the increased number of inclusions present on the membrane of Myo5b KO enteroids and explants following inhibition of dynamin with Dyngo treatment.…”

Section: Discussionsupporting

confidence: 86%

Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Engevik

Kaji

Postema

et al. 2019

Journal of Cell Biology

View full text Add to dashboard Cite

In patients with inactivating mutations in myosin Vb (Myo5B), enterocytes show large inclusions lined by microvilli. The origin of inclusions in small-intestinal enterocytes in microvillus inclusion disease is currently unclear. We postulated that inclusions in Myo5b KO mouse enterocytes form through invagination of the apical brush border membrane. 70-kD FITC-dextran added apically to Myo5b KO intestinal explants accumulated in intracellular inclusions. Live imaging of Myo5b KO–derived enteroids confirmed the formation of inclusions from the apical membrane. Treatment of intestinal explants and enteroids with Dyngo resulted in accumulation of inclusions at the apical membrane. Inclusions in Myo5b KO enterocytes contained VAMP4 and Pacsin 2 (Syndapin 2). Myo5b;Pacsin 2 double-KO mice showed a significant decrease in inclusion formation. Our results suggest that apical bulk endocytosis in Myo5b KO enterocytes resembles activity-dependent bulk endocytosis, the primary mechanism for synaptic vesicle uptake during intense neuronal stimulation. Thus, apical bulk endocytosis mediates the formation of inclusions in neonatal Myo5b KO enterocytes.

show abstract

Section: Discussionsupporting

confidence: 86%

Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Engevik

Kaji

Postema

et al. 2019

Journal of Cell Biology

View full text Add to dashboard Cite

show abstract

“…A similar association is observed with the expression levels of protein markers, i.e. S100A4 that is known to promote angiogenesis and metastasis development (50), and VGFR2 that plays a fundamental role in neovascularization (51). These found associations were consistent regardless of the type of tumor, treatment naïve glioma or recurrent GBM.…”

Section: Resultssupporting

confidence: 60%

Tumor cell phenotype and heterogeneity differences in IDH1 mutant vs wild-type gliomas

Berens

Sood²,

Barnholtz‐Sloan

et al. 2019

Preprint

View full text Add to dashboard Cite

34Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition 35 and cellular interactions have not been well characterized. To gain new clinical-and biological-insights 36 into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated 37 multiplexed immunofluorescence single cell data for 43 protein markers across cancer hallmarks, in 38 addition to cell spatial metrics, genomic sequencing and magnetic resonance imaging (MRI) quantitative 39 features. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion differ between 40 IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted 41 in the MR imaging features of peritumoral edema and contrast enhancement volumes. Longer overall 42 survival for IDH1mt glioma patients may reflect generalized altered cellular, molecular, spatial 43 heterogeneity which manifest in discernable radiological manifestations. 44 45 48 While gliomas are relatively rare in the general population with an average annual age-adjusted 49 incidence of 6.2 per 100,000, these primary brain tumors contribute significant morbidity and mortality, 50 with glioblastoma carrying a 5-year survival rate of less than 6%(1). 51 52 The landscape of our knowledge about molecular features required for accurate diagnosis and prognosis 53 for glioma patients has advanced greatly in the last decade (2-5). Molecular subclassification highlights 54 different genetic underpinnings of glioblastoma (6), which offer some prognostic insight (7), likely 55 attributable, in part, to gene expression patterns influencing vulnerability to radiation (8). The World 56 Health Organization (WHO) classifies gliomas into defined categories based upon histologic and 57 molecular features and are assigned into four grades of increasing aggressiveness. Additionally, the 58 methylation status of O6-methylguanine-DNA methyltransferase (MGMT) has been implicated as a 59 useful biomarker for conferring tumor resistance to alkylating chemotherapies; methylation of the 60 MGMT promoter leads to transcriptional silencing of MGMT, which is associated with loss of MGMT 61 expression and increased response to alkylating chemotherapies such as temozolomide (TMZ) (9). 62 Analysis of DNA methylation from gliomas identified a DNA methylation-based phenotype, G-CIMP, 63 which is characterized by global hypermethylation of CpG islands and is predictive of increased survival; 64 this G-CIMP phenotype is associated with isocitrate dehydrogenase (IDH) mutation status (3, 4, 10). 4 65 66 IDH wild type (wt) in histologically defined low-grade gliomas is associated with poor clinical prognosis 67 that more resembles glioblastoma multiforme (GBM), which generally lack IDH mutation (IDHmt) (3, 11). 68 Conversely, IDH mutations are observed in the majority of lower-grade gliomas and are associated with 69 better clinical outcomes. In low-grade gliomas with IDH mutations, 1p/19q codeletion is further 70 associated wit...

show abstract

“…The encoded protein has roles in cytoskeletal remodeling and cell migration, and is a binding partner of CDC42, a GTPase essential for VEGF signaling and developmental processes. 25,26 In two unrelated families with HLHS, we identified compound heterozygous variants in VASP or TLN2, respectively ( Table 3). Both genes are involved in mechanotransduction of developing cardiomyocytes, linking mechanical strain and cardiac remodeling.…”

Section: Novel Candidate Genesmentioning

confidence: 99%

The Cardiac Genome Clinic: implementing genome sequencing in pediatric heart disease

Reuter

Chaturvedi

Liston

et al. 2020

Genetics in Medicine

View full text Add to dashboard Cite

Purpose This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease. Methods We analyzed genome sequencing data of 111 families with cardiac lesions for rare, disease-associated variation. Results In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1) and six were inherited from parents with no or subclinical heart phenotypes (FLT4, DNAH9, MYH11, NEXMIF, NIPBL, PTPN11). Outcome of the testing was associated with the presence of extracardiac features (p = 0.02), but not a positive family history for cardiac lesions (p = 0.67). We also report novel plausible gene–disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis. Conclusion This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene–disease associations.

show abstract

VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis

Cited by 31 publications

References 28 publications

Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Tumor cell phenotype and heterogeneity differences in IDH1 mutant vs wild-type gliomas

The Cardiac Genome Clinic: implementing genome sequencing in pediatric heart disease

Contact Info

Product

Resources

About