Evidence map›Paper›PMID 25955407›Full record

ArticleAmerican journal of respiratory cell and molecular biology2015

Role of Exchange Protein Activated by cAMP 1 in Regulating Rates of Microtubule Formation in Cystic Fibrosis Epithelial Cells.

Sharon M Rymut, Tracy Ivy, Deborah A Corey, Calvin U Cotton, James D Burgess, Thomas J Kelley

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. HDAC6 inhibition reducesInfection and immunity · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Carbonic anhydrase and soluble adenylate cyclase regulation of cystic fibrosis cellular phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2022
    Article
  7. Article
  8. Article
  9. Resveratrol restores intracellular transport in cystic fibrosis epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Electrochemical measurement of membrane cholesterol correlates with CFTR function and is HDAC6-dependent.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2019
    Article
  15. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2016
    Article
  16. Review
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

6 authors at 2 institutions in 1 country.

Sharon M RymutDepartments of 1 Pharmacology.
Tracy Ivy2 Pediatrics, and.
Deborah A Corey2 Pediatrics, and.
Calvin U Cotton2 Pediatrics, and.
James D Burgess3 Chemistry, Case Western Reserve University, Cleveland, Ohio.
Thomas J KelleyDepartments of 1 Pharmacology.
Pediatrics and Genetics · USCase Western Reserve University · US

Funding

Translational Research in Cystic FibrosisP30DK027651 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI DRUMM, MITCHELL L · 1986 to 2014
$15.6M
Dysregulation of Nrf2 in CF epitheliaR01HL109362 · NHLBI · EMORY UNIVERSITY · PI ZIADY, ASSEM G · 2011 to 2014
$1.5M
Diagnostic Cholesterol Efflux from Nasal Membrane in Cystic FibrosisR01EB009481 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI BURGESS, JAMES D · 2011 to 2014
$1.3M
CYTO VISION WORKSTATION FOR USE IN MULTI-USER FACILITY: CYSTIC FIBROSISS10RR021228 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI CONRAD, PATRICIA A · 2005 to 2005
$178k
NCRR NIH HHS S10 RR021228NHLBI NIH HHS R01 HL109362NHLBI NIH HHS R01HL109362NIBIB NIH HHS R01 EB009481NIBIB NIH HHS R01EB009481NIDDK NIH HHS 2P30DK027651NIDDK NIH HHS P30 DK027651
6 · The paper itself

Abstract

The regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells and the consequences of reduced rates of microtubule polymerization on downstream CF cellular events, such as cholesterol accumulation, a marker of impaired intracellular transport, are explored here. It is identified that microtubules in both CF cell models and in primary CF nasal epithelial cells repolymerize at a slower rate compared with respective controls. Previous studies suggest a role for cAMP in modulating organelle transport in CF cells, implicating a role for exchange protein activated by cAMP (EPAC) 1, a regulator of microtubule elongation, as a potential mechanism. EPAC1 activity is reduced in CF cell models and in Cftr(-/-) mouse lung compared with respective non-CF controls. Stimulation of EPAC1 activity with the selective EPAC1 agonist, 8-cpt-2-O-Me-cAMP, stimulates microtubule repolymerization to wild-type rates in CF cells. EPAC1 activation also alleviates cholesterol accumulation in CF cells, suggesting a direct link between microtubule regulation and intracellular transport. To verify the relationship between transport and microtubule regulation, expression of the protein, tubulin polymerization-promoting protein, was knocked down in non-CF human tracheal (9/HTEo(-)) cells to mimic the microtubule dysregulation in CF cells. Transduced cells with short hairpin RNA targeting tubulin polymerization-promoting protein exhibit CF-like perinuclear cholesterol accumulation and other cellular manifestations of CF cells, thus supporting a role for microtubule regulation as a mechanism linking CFTR function to downstream cellular manifestation.

Indexed as

AnimalsCell LineCyclic AMPCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGuanine Nucleotide Exchange FactorsHumansKineticsMice, KnockoutMicrotubulesProtein MultimerizationRespiratory MucosaCFTR protein, humanCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorGuanine Nucleotide Exchange FactorsRAPGEF3 protein, humancholesterolcystic fibrosisexchange protein activated by cAMP 1microtubulesRap1

Identifiers

PMID25955407
PMCPMC4742938
OpenAlexW1958550671

What OpenQuestion holds

Textmetadata
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.