Evidence map›Paper›PMID 21995445›Full record

ArticleThe Biochemical journal2012

Dab2 is a key regulator of endocytosis and post-endocytic trafficking of the cystic fibrosis transmembrane conductance regulator.

Lianwu Fu, Andras Rab, Li Ping Tang, Steven M Rowe, Zsuzsa Bebok, James F Collawn

Abstract read
In one paragraph

Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.2field-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

31 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Article
  8. Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Effects ofAmerican journal of physiology. Cell physiology · 2017
    Review
  18. Review
  19. Article
  20. Article
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 1 institution in 1 country.

Lianwu FuDepartment of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. lianwufu@uab.edu
Andras Rab
Li Ping Tang
Steven M Rowe
Zsuzsa Bebok
James F Collawn
University of Alabama at Birmingham · US

Funding

UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMIT GAGGAR · 2007 to 2026
$23.0M
Cell Biology of CFTR in Polarized EpitheliaR01DK060065 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI COLLAWN, JAMES F. · 2003 to 2013
$3.1M
CFTR Biogenesis and Function in EpitheliaR01HL076587 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BEBOK, ZSUZSA · 2004 to 2012
$2.6M
Premature Termination Codon SuppressionK23DK075788 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2006 to 2010
$638k
NHLBI NIH HHS R01 HL076587NIDDK NIH HHS K23 DK075788NIDDK NIH HHS P30 DK 072482NIDDK NIH HHS P30 DK072482NIDDK NIH HHS R01 DK060065NIDDK NIH HHS R01 DK60065
6 · The paper itself

Abstract

CFTR (cystic fibrosis transmembrane conductance regulator) is expressed in the apical membrane of epithelial cells. Cell-surface CFTR levels are regulated by endocytosis and recycling. A number of adaptor proteins including AP-2 (μ2 subunit) and Dab2 (Disabled-2) have been proposed to modulate CFTR internalization. In the present study we have used siRNA (small interfering RNA)-mediated silencing of these adaptors to test their roles in the regulation of CFTR cell-surface trafficking and stability in human airway epithelial cells. The results indicate that μ2 and Dab2 performed partially overlapping, but divergent, functions. While μ2 depletion dramatically decreased CFTR endocytosis with little effect on the half-life of the CFTR protein, Dab2 depletion increased the CFTR half-life ~3-fold, in addition to inhibiting CFTR endocytosis. Furthermore, Dab2 depletion inhibited CFTR trafficking from the sorting endosome to the recycling compartment, as well as delivery of CFTR to the late endosome, thus providing a mechanistic explanation for increased CFTR expression and half-life. To test whether two E3 ligases were required for the endocytosis and/or down-regulation of surface CFTR, we siRNA-depleted CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting protein] and c-Cbl (casitas B-lineage lymphoma). We demonstrate that CHIP and c-Cbl depletion have no effect on CFTR endocytosis, but c-Cbl depletion modestly enhanced the half-life of CFTR. The results of the present study define a significant role for Dab2 both in the endocytosis and post-endocytic fate of CFTR.

Indexed as

Adaptor Protein Complex 2Adaptor Protein Complex mu SubunitsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCells, CulturedCystic Fibrosis Transmembrane Conductance RegulatorEndocytosisHumansProtein TransportProto-Oncogene Proteins c-cblRNA, Small InterferingTumor Suppressor ProteinsUbiquitin-Protein LigasesAdaptor Protein Complex 2adaptor protein complex 2, mu 2 subunitAdaptor Protein Complex mu SubunitsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCBL protein, humanCystic Fibrosis Transmembrane Conductance RegulatorDAB2 protein, humanProto-Oncogene Proteins c-cblRNA, Small InterferingSTUB1 protein, humanTumor Suppressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID21995445
PMCPMC3646389
OpenAlexW2080047517

What OpenQuestion holds

Textmetadata
LicenceTDM
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.