Evidence map›Paper›PMID 37721936›Full record

ArticlePLoS genetics2023

The proprotein convertase BLI-4 promotes collagen secretion prior to assembly of the Caenorhabditis elegans cuticle.

Susanna K Birnbaum, Jennifer D Cohen, Alexandra Belfi, John I Murray, Jennifer R G Adams, Andrew D Chisholm, Meera V Sundaram

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-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

18 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. A Lipocalin and a Hedgehog-related protein are partners in thebioRxiv : the preprint server for biology · 2026
    Article
  3. Pre-cuticle DPY-6 acts as a blueprint for aECM periodic organization inbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. MLT-11 is necessary forbioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The NHR-23-regulated putative protease inhibitorbioRxiv : the preprint server for biology · 2024
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. bioRxiv : the preprint server for biology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Susanna K BirnbaumDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-8895-5976
Jennifer D CohenDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-7810-7666
Alexandra BelfiDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-9237-5085
John I MurrayDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0003-4026-584X
Jennifer R G AdamsDepartments of Neurobiology and Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.ORCID 0000-0002-7517-1256
Andrew D ChisholmDepartments of Neurobiology and Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, San Diego, California, United States of America.ORCID 0000-0001-5091-0537
Meera V SundaramDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-2940-8750
University of Pennsylvania · USUniversity of California San Diego · US

Funding

Penn Dermatology Research Training ProgramT32AR007465 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI Elizabeth Anne Grice, David Joel Margolis · 1986 to 2026
$9.0M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Building and shaping the apical extracellular matrixR35GM136315 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Meera Sundaram · 2020 to 2026
$4.7M
Maintenance and Repair of the C. elegans SkinR35GM134970 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHISHOLM, ANDREW D · 2020 to 2024
$2.1M
Decoding lineage and fate specification in the C. elegans embryoR35GM127093 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI MURRAY, JOHN ISAAC · 2018 to 2022
$2.0M
NIAMS NIH HHS T32 AR007465NIGMS NIH HHS R35 GM127093NIGMS NIH HHS R35 GM134970NIGMS NIH HHS R35 GM136315NIH HHS P40 OD010440
6 · The paper itself

Abstract

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsSubtilisinAmino Acid SequenceAnimalsCollagenProprotein ConvertasesSubtilisinsbli-4 protein, C elegansCaenorhabditis elegans ProteinsCollagenProprotein ConvertasesSubtilisinSubtilisins

Identifiers

PMID37721936
PMCPMC10538796
OpenAlexW4386825714

What OpenQuestion holds

Textmetadata
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.