Evidence map›Paper›PMID 40608550›Full record

ArticleThe FEBS journal2025

Impact of N-linked glycans on the dual short fibulin/LTBP-4 axes regulating elastogenesis.

Valentin Nelea, Heena Kumra, Chae Syng Lee, Daniel Williamson, Hana Hakami, Rong-Mo Zhang, Neha E H Dinesh, Robert Haltiwanger, Dieter P Reinhardt

Abstract read
In one paragraph

Article in The FEBS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Valentin NeleaDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Heena KumraDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.ORCID https://orcid.org/0000-0001-7065-6716
Chae Syng LeeDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Daniel WilliamsonComplex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
Hana HakamiDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Rong-Mo ZhangDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Neha E H DineshDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Robert HaltiwangerComplex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
Dieter P ReinhardtDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.ORCID https://orcid.org/0000-0001-6535-9872

Funding

O-glycosylation of cysteine-rich modulesR35GM148433 · NIGMS · UNIVERSITY OF GEORGIA · PI Robert S. Haltiwanger · 2023 to 2026
$1.8M
Genetic Aortic Disorders Association CanadaNatural Sciences and Engineering Research Council of Canada RGPIN-2022-05045NIGMS NIH HHS R35 GM148433NIGMS NIH HHS R35GM148433
6 · The paper itself

Abstract

Elastic fibers are key extracellular components, providing elasticity to blood vessels, lungs, skin, and bladder. Elastic fiber formation requires the accessory proteins fibulin-4, fibulin-5, and the long and short isoforms of the latent TGFβ binding protein-4 (LTBP-4L/S). We established two molecular axes, LTBP-4L/fibulin-4 and LTBP-4S/fibulin-5, defined similar and distinct functions, and determined the role of N-linked glycans in this context. Glycoproteomic analysis identified the specific N-linked glycans in these proteins. Biophysical analyses revealed that the N-linked glycans of LTBP-4L, but not fibulin-4, were critical for fibulin-4-mediated conformational extension of LTBP-4L, impacting its function and assembly. Biochemical and recombinant removal of N-linked glycans from fibulin-4 enhanced its interaction with tropoelastin and elastic fiber formation, indicating an inhibitory role for these N-glycans. Fibulin-5 strongly interacted with and robustly induced a conformational extension of LTBP-4S, leading to enhanced binding to fibronectin, increased LTBP-4S deposition, and doubling of elastic fiber formation. Loss of N-linked glycans from fibulin-5, but not LTBP-4S, reduced their interaction by about 10-fold and abolished the ability of fibulin-5 to extend LTBP-4S conformationally. The presence of fibulin-5-extended LTBP-4S did not trigger tropoelastin aggregation in an in vitro assembly assay but boosted elastic fiber-like assembly massively when fibulin-4 and LTBP-4L were additionally present, suggesting synergistic effects. N-linked glycans in fibulin-5 were essential in this process. The study uncovers novel mechanisms that regulate elastic fiber formation, including overlapping and distinct roles of the LTBP-4L/fibulin-4 and the LTBP-4S/fibulin-5 axes and the importance of N-linked glycans of each of these proteins.

Indexed as

Elastic TissueExtracellular Matrix ProteinsLatent TGF-beta Binding ProteinsPolysaccharidesAnimalsHumansProtein BindingTropoelastinExtracellular Matrix ProteinsFBLN5 protein, humanLatent TGF-beta Binding ProteinsLTBP4 protein, humanPolysaccharidesTropoelastinelastinelastogenesisLTBP‐4N‐glycanssmall fibulins

Identifiers

PMID40608550
PMCPMC12527114

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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.