Evidence map›Paper›PMID 25008321›Full record

ArticleThe Journal of biological chemistry2014

Vesicle-associated membrane protein 2 (VAMP2) but Not VAMP3 mediates cAMP-stimulated trafficking of the renal Na+-K+-2Cl- co-transporter NKCC2 in thick ascending limbs.

Paulo S Caceres, Mariela Mendez, Pablo A Ortiz

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Transcriptome Study of 2 Black Cohorts RevealsJournal of the American Heart Association · 2024
    Article
  3. Review
  4. Article
  5. Molecular regulation of NKCC2 in blood pressure control and hypertension.Current opinion in nephrology and hypertension · 2019
    Review
  6. Superoxide increases surface NKCC2 in the rat thick ascending limbs via PKC.American journal of physiology. Renal physiology · 2019
    Article
  7. Article
  8. AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro.Investigative ophthalmology & visual science · 2017
    Article
  9. Regulation of renal Na-(K)-Cl cotransporters by vasopressin.Pflugers Archiv : European journal of physiology · 2017
    Review
  10. CaThe Journal of biological chemistry · 2017
    Article
  11. Article
  12. Article
  13. 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

3 authors at 1 institution in 1 country.

Paulo S CaceresFrom the Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202 and the Department of Physiology, Wayne State University, Detroit, Michigan 48202.
Mariela MendezFrom the Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202 and.
Pablo A OrtizFrom the Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202 and the Department of Physiology, Wayne State University, Detroit, Michigan 48202 portiz1@hfhs.org.
Henry Ford Hospital · US

Funding

Salt Absorption by the THAL: Role of NKCC2 traffickingR01HL080409 · NHLBI · HENRY FORD HEALTH SYSTEM · PI ORTIZ, PABLO A. · 2006 to 2010
$1.3M
Molecular Mechanism of Renin Release, Role of SNAREsF32HL096346 · NHLBI · HENRY FORD HEALTH SYSTEM · PI MENDEZ, MARIELA · 2009 to 2011
$168k
NHLBI NIH HHS F32 HL096346NHLBI NIH HHS F32HL096346-01NHLBI NIH HHS R01 HL080409
6 · The paper itself

Abstract

In the kidney, epithelial cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na(+)/K(+)/2Cl(-) co-transporter NKCC2. Steady-state surface NKCC2 levels in the apical membrane are maintained by a balance between exocytic delivery, endocytosis, and recycling. cAMP is the second messenger of hormones that enhance NaCl absorption. cAMP stimulates NKCC2 exocytic delivery via protein kinase A (PKA), increasing steady-state surface NKCC2. However, the molecular mechanism involved has not been studied. We found that several members of the SNARE family of membrane fusion proteins are expressed in TALs. Here we report that NKCC2 co-immunoprecipitates with VAMP2 in rat TALs, and they co-localize in discrete domains at the apical surface. cAMP stimulation enhanced VAMP2 exocytic delivery to the plasma membrane of renal cells, and stimulation of PKA enhanced VAMP2-NKCC2 co-immunoprecipitation in TALs. In vivo silencing of VAMP2 but not VAMP3 in TALs blunted cAMP-stimulated steady-state surface NKCC2 expression and completely blocked cAMP-stimulated NKCC2 exocytic delivery. VAMP2 was not involved in constitutive NKCC2 delivery. We concluded that VAMP2 but not VAMP3 selectively mediates cAMP-stimulated NKCC2 exocytic delivery and surface expression in TALs. We also demonstrated that cAMP stimulation enhances VAMP2 exocytosis and promotes VAMP2 interaction with NKCC2.

Indexed as

AnimalsCells, CulturedCyclic AMPExocytosisGene SilencingKidneyPhosphorylationProtein TransportRatsSNARE ProteinsSolute Carrier Family 12, Member 1Vesicle-Associated Membrane Protein 2Vesicle-Associated Membrane Protein 3Cyclic AMPSlc12a1 protein, ratSNARE ProteinsSolute Carrier Family 12, Member 1Vamp2 protein, ratVesicle-Associated Membrane Protein 2Vesicle-Associated Membrane Protein 3vesicle-associated membrane protein 3, ratCyclic AMP (cAMP)Epithelial CellEpithelial Sodium TransportExocytosisKidneyMembrane TraffickingNa-K-Cl Co-transporter 2 (NKCC2)SNARE Proteins

Identifiers

PMID25008321
PMCPMC4156046
OpenAlexW2031184481

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.