Evidence map›Paper›PMID 21430287›Full record

ArticleAmerican journal of physiology. Cell physiology2011

NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileum.

Rakhilya Murtazina, Olga Kovbasnjuk, Tian-E Chen, Nicholas C Zachos, Yeuping Chen, Hetal S Kocinsky, Boris M Hogema, Ursula Seidler, Hugo R de Jonge, Mark Donowitz

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

34 citing papers in PubMed, 40 citations in OpenAlex.

  1. Cystinosin regulates NaEMBO reports · 2026
    Article
  2. Article
  3. Cystinosin is involved in NabioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. NHERF3 is necessary forAmerican journal of physiology. Cell physiology · 2019
    Article
  11. Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018
    Article
  12. The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018
    Review
  13. Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018
    Article
  14. Review
  15. Phosphorylation of NHE3-SMolecular biology of the cell · 2017
    Article
  16. Phosphorylation and subcellular localization of NaJournal of physiology and biochemistry · 2017
    Article
  17. Article
  18. Secretory diarrhoea: mechanisms and emerging therapies.Nature reviews. Gastroenterology & hepatology · 2015
    Review
  19. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3.American journal of physiology. Renal physiology · 2015
    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

10 authors at 4 institutions in 3 countries.

Rakhilya MurtazinaDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Olga Kovbasnjuk
Tian-E Chen
Nicholas C Zachos
Yeuping Chen
Hetal S Kocinsky
Boris M Hogema
Ursula Seidler
Hugo R de Jonge
Mark Donowitz
Erasmus MC · NLJohns Hopkins University · USMedizinische Hochschule Hannover · DEYale University · US

Funding

Two-Photon Microscopy Imaging CoreP01DK072084 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HUBBARD, ANN · 2006 to 2013
$12.7M
DIARRHEAL DISEASES: A PHYSIOLOGIC APPROACH TO TREATMENTR01DK026523 · NIDDK · TUFTS MEDICAL CENTER · PI DONOWITZ, MARK · 1986 to 2016
$7.8M
PDZ Domain Proteins and NHE3 RegulationR01DK061765 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK, TSE, CHUNG-MING · 2004 to 2013
$4.7M
Hopkins Digestive Diseases Research Development CenterR24DK064388 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2003 to 2010
$4.6M
PLCgamma regulates HNE3 activity through direct binding and dynamic complexesK01DK080930 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2008 to 2011
$587k
Intracellular Calcium Regulated NHE3 EndocytosisR03DK091482 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2012
$164k
NIDDK NIH HHS K01 DK080930NIDDK NIH HHS P01DK072084NIDDK NIH HHS R01 DK061765NIDDK NIH HHS R01DK26523NIDDK NIH HHS R01DK61765NIDDK NIH HHS R03 DK091482NIDDK NIH HHS R24DK64388NIDDK NIH HHS T32DK2007632
6 · The paper itself

Abstract

To test the hypothesis that Na(+)/H(+) exchanger (NHE) regulatory factor 2 (NHERF2) is necessary for multiple aspects of acute regulation of NHE3 in intact mouse small intestine, distal ileal NHE3 activity was determined using two-photon microscopy/SNARF-4F in a NHERF2-null mouse model. The NHERF2-null mouse ileum had shorter villi, deeper crypts, and decreased epithelial cell number. Basal rates of NHE3 activity were reduced in NHERF2-null mice, which was associated with a reduced percentage of NHE3 in the apical domain and an increase in intracellular NHE3 amount but no change in total level of NHE3 protein. cAMP, cGMP, and elevated Ca(2+) due to apical exposure to UTP all inhibited NHE3 activity in wild-type mouse ileum but not in NHERF2-null mice, while inhibition by hyperosmolarity occurred normally. The cAMP-increased phosphorylation of NHE3 at aa 552; levels of PKAIIα and cGMP-dependent protein kinase II (cGKII); and elevation of Ca(2+) were similar in wild-type and NHERF2-null mouse ileum. Luminal lysophosphatidic acid (LPA) stimulated NHE3 in wild-type but not in NHERF2-null ileum. In conclusion, 1) there are subtle structural abnormalities in the small intestine of NHERF2-null mouse which include fewer villus epithelial cells; 2) the decreased basal NHE3 activity and reduced brush border NHE3 amount in NHERF2-null mice show that NHERF2 is necessary for normal basal trafficking or retention of NHE3 in the apical domain; 3) hyperosmolar inhibition of NHE3 occurs similarly in wild-type and NHERF2-null ileum, demonstrating that some inhibitory mechanisms of NHE3 are not NHERF2 dependent; 4) cAMP inhibition of NHE3 is NHERF2 dependent at a step downstream of cAMP/PKAII phosphorylation of NHE3 at aa 552; 5) cGMP- and UTP-induced inhibition of NHE3 are NHERF2 dependent at steps beyond cGKII and the UTP-induced increase of intracellular Ca(2+); and 6) LPA stimulation of NHE3 is also NHERF2 dependent.

Indexed as

Second Messenger SystemsAnimalsCalciumCell ProliferationCells, CulturedCyclic AMPCyclic GMPEpithelial CellsIleumLysophospholipidsMaleMiceMice, Inbred C57BLMice, KnockoutMicrovilliOsmolar ConcentrationCalciumCyclic AMPCyclic GMPlysophosphatidic acidLysophospholipidsPhosphoproteinsSlc9a3 protein, mouseSodium-Hydrogen Exchanger 3sodium-hydrogen exchanger regulatory factorSodium-Hydrogen Exchangers

Identifiers

PMID21430287
PMCPMC3129824
OpenAlexW2138464039

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.