Evidence map›Paper›PMID 33956260›Full record

ArticleAngiogenesis2021

Notch regulates vascular collagen IV basement membrane through modulation of lysyl hydroxylase 3 trafficking.

Stephen J Gross, Amelia M Webb, Alek D Peterlin, Jessica R Durrant, Rachel J Judson, Qanber Raza, Jan K Kitajewski, Erich J Kushner

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Angiogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022
    Review
  16. Article
  17. [JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
    Article
  18. Review
  19. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Stephen J GrossDepartment of Biological Sciences, University of Denver, Denver, CO, 80210, USA.
Amelia M WebbDepartment of Biological Sciences, University of Denver, Denver, CO, 80210, USA.
Alek D PeterlinDepartment of Biological Sciences, University of Denver, Denver, CO, 80210, USA.
Jessica R DurrantHistoTox Labs, Boulder, CO, USA.
Rachel J JudsonDepartment of Biological Sciences, University of Denver, Denver, CO, 80210, USA.
Qanber RazaDepartment of Physiology and Biophysics, University of Illinois, Chicago, IL, USA.
Jan K KitajewskiDepartment of Physiology and Biophysics, University of Illinois, Chicago, IL, USA.
Erich J KushnerDepartment of Biological Sciences, University of Denver, Denver, CO, 80210, USA. Erich.Kushner@du.edu.
University of Denver · USUniversity of Illinois Chicago · US

Funding

Notch in Angiogenesis and Vascular BiologyR01HL112626 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Jan K. Kitajewski · 2012 to 2026
$6.3M
Centrosomes and Cytoskeletal Mechanisms of Blood Vessel DysfunctionR00HL124311 · NHLBI · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI KUSHNER, ERICH J · 2017 to 2019
$746k
Mechanisms of Delta-like 4 Endocytosis and Notch Activation During Blood Vessel DevelopmentR15HL156106 · NHLBI · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI KUSHNER, ERICH J · 2021 to 2021
$439k
Mechanisms of Basement Membrane Regulation During AngiogenesisR56HL148450 · NHLBI · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI KUSHNER, ERICH J · 2019 to 2019
$372k
NHLBI NIH HHS 1R56HL148450-01NHLBI NIH HHS R00 HL124311NHLBI NIH HHS R00HL124311NHLBI NIH HHS R01 HL112626NHLBI NIH HHS R15 HL156106NHLBI NIH HHS R56 HL148450
6 · The paper itself

Abstract

Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development using both in vitro imaging and biochemistry as well as in vivo models. Knockdown of Rab10 reduced de novo Col IV secretion in vivo and in vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 results in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrate that Rab10 is Notch responsive, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune basement membrane secretion during blood vessel development.

Indexed as

Collagen Type IVProcollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseBasement MembraneEndothelial CellsMorphogenesisCollagen Type IVProcollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseAngiogenesisBlood vesselsCollagen IVDevelopmentLysyl hydroxlyase 3Notch1Rab10Rab25SecretionSmall vessel diseaseTraffickingZebrafish

Identifiers

PMID33956260
PMCPMC8487879
OpenAlexW3158548556

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.