ArticleMolecular and cellular biology2015
Requisite role for Nck adaptors in cardiovascular development, endothelial-to-mesenchymal transition, and directed cell migration.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development.Journal of mammary gland biology and neoplasia · 2023Article
- NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Actin cytoskeleton in angiogenesis.Biology open · 2022Review
- Endothelial NCK2 promotes atherosclerosis progression in male but not femaleFrontiers in cardiovascular medicine · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- Review
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- ShcA expression in podocytes is dispensable for glomerular development but its upregulation is associated with kidney disease.American journal of translational research · 2021Article
- Selective role of Nck1 in atherogenic inflammation and plaque formation.The Journal of clinical investigation · 2020Article
- Nck1 is a critical adaptor between proatherogenic blood flow, inflammation, and atherosclerosis.The Journal of clinical investigation · 2020Article
- Identification of differentially expressed circular RNAs during TGF-ß1-induced endothelial-to-mesenchymal transition in rat coronary artery endothelial cells.Anatolian journal of cardiology · 2018Article
- Nck deficiency is associated with delayed breast carcinoma progression and reduced metastasis.Molecular biology of the cell · 2017Article
- Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis.Frontiers in cardiovascular medicine · 2017Review
- Nephrin Tyrosine Phosphorylation Is Required to Stabilize and Restore Podocyte Foot Process Architecture.Journal of the American Society of Nephrology : JASN · 2016Article
- Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization.Circulation · 2016Article
- Actin remodeling by Nck regulates endothelial lumen formation.Molecular biology of the cell · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Development of the cardiovascular system is critically dependent on the ability of endothelial cells (ECs) to reorganize their intracellular actin architecture to facilitate migration, adhesion, and morphogenesis. Nck family cytoskeletal adaptors function as key mediators of actin dynamics in numerous cell types, though their role in EC biology remains largely unexplored. Here, we demonstrate an essential requirement for Nck within ECs. Mouse embryos lacking endothelial Nck1/2 expression develop extensive angiogenic defects that result in lethality at about embryonic day 10. Mutant embryos show immature vascular networks, with decreased vessel branching, aberrant perivascular cell recruitment, and reduced cardiac trabeculation. Strikingly, embryos deficient in endothelial Nck also fail to undergo the endothelial-to-mesenchymal transition (EnMT) required for cardiac valve morphogenesis, with loss of Nck disrupting expression of major EnMT markers, as well as suppressing mesenchymal outgrowth. Furthermore, we show that Nck-null ECs are unable to migrate downstream of vascular endothelial growth factor and angiopoietin-1, and they exhibit profound perturbations in cytoskeletal patterning, with disorganized cellular projections, impaired focal adhesion turnover, and disrupted actin-based signaling. Our collective findings thereby reveal a crucial role for Nck as a master regulator within the endothelium to control actin cytoskeleton organization, vascular network remodeling, and EnMT during cardiovascular development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.