Evidence map›Paper›PMID 32134975›Full record

ArticlePloS one2020

Munc13 mediates klotho-inhibitable diacylglycerol-stimulated exocytotic insertion of pre-docked TRPC6 vesicles.

Jian Xie, Sung-Wan An, Xin Jin, Yuan Gui, Chou-Long Huang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024
    Review
  2. Review
  3. Review
  4. Soluble αKlotho downregulates Orai1-mediated store-operated CaPflugers Archiv : European journal of physiology · 2021
    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

5 authors at 1 institution in 1 country.

Jian XieDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Sung-Wan AnDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Xin JinDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Yuan GuiDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Chou-Long HuangDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0001-9963-3040
University of Iowa · US

Funding

Klotho and Chronic Kidney DiseaseR01DK100605 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, CHOU-LONG · 2014 to 2023
$3.5M
Regulation of Renal Calcium Transport in Health and DiseaseR01DK109887 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, CHOU-LONG · 2016 to 2020
$1.8M
NIDDK NIH HHS R01 DK100605NIDDK NIH HHS R01 DK109887
6 · The paper itself

Abstract

α-Klotho is a type 1 transmembrane protein that exhibits aging suppression function. The large amino-terminal extracellular domain of α-klotho is shed as soluble klotho (sKlotho) and functions as a circulating cardioprotective hormone. Diacylglycerol (DAG)-activated calcium-permeable TRPC6 channel plays a critical role in stress-induced cardiac remodeling. DAG activates TRPC6 by acting directly on the channel to increase its activity and by stimulation of channel exocytosis. sKlotho protects the heart by inhibiting DAG stimulation of TRPC6 exocytosis. How DAG stimulates TRPC6 exocytosis and thereby inhibition by sKlotho are unknown. Using a compound that directly activates TRPC6 without affecting channel exocytosis, we validate that sKlotho selectively blocks DAG stimulation of channel exocytosis. We further show that DAG stimulates exocytosis of TRPC6-containing vesicles pre-docked to the plasma membrane. Mnuc13 family proteins play important roles in the proper assembly of SNARE proteins and priming the vesicle competent for fusion. We show that DAG stimulates TRPC6 exocytosis by targeting to the C1 domain of Munc13-2. The results provide fresh insights into the molecular mechanism by which DAG regulates vesicle fusion and how sKlotho protects the heart against injury.

Indexed as

Cell MembraneDiglyceridesExocytosisGlucuronidaseHEK293 CellsHumansKlotho ProteinsMembrane FusionNerve Tissue ProteinsTRPC6 Cation Channel1,2-diacylglycerolDiglyceridesGlucuronidaseKlotho ProteinsNerve Tissue ProteinsTRPC6 Cation ChannelTRPC6 protein, humanUNC13B protein, human

Identifiers

PMID32134975
PMCPMC7058344
OpenAlexW3009071565

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.