Evidence map›Paper›PMID 36936781›Full record

ArticleiScience2023

Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation.

Sumita Mishra, Junfeng Ma, Desirae McKoy, Masayuki Sasaki, Federica Farinelli, Richard C Page, Mark J Ranek, Natasha Zachara, David A Kass

Open access · goldFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.6field-weighted citation impact, top 38% 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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

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

9 authors at 3 institutions in 1 country.

Sumita MishraDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Junfeng MaDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Desirae McKoyDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Masayuki SasakiDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Federica FarinelliDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Richard C PageDepartment of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.
Mark J RanekDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Natasha ZacharaDepartment of Biological Chemistry, Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
David A KassDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins University · USGeorgetown University · USMiami University · US

Funding

Leveraging Protein Kinase G-1 Nanodomain Control and Molecular Targeting to Enhance its Therapeutic Use Against Myocardial DiseaseR35HL135827 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KASS, DAVID ALAN · 2017 to 2023
$6.3M
Triage mechanisms for directing protein refolding and degradationR35GM128595 · NIGMS · MIAMI UNIVERSITY OXFORD · PI Richard C Page · 2018 to 2026
$2.8M
NHLBI NIH HHS R35 HL135827NIGMS NIH HHS R35 GM128595
6 · The paper itself

Abstract

Transient receptor potential canonical type 6 (TRPC6) is a non-voltage-gated channel that principally conducts calcium. Elevated channel activation contributes to fibrosis, hypertrophy, and proteinuria, often coupled to stimulation of nuclear factor of activated T-cells (NFAT). TRPC6 is post-translationally regulated, but a role for O-linked β-N-acetyl glucosamine (O-GlcNAcylation) as elevated by diabetes, is unknown. Here we show TRPC6 is constitutively O-GlcNAcylated at Ser14, Thr70, and Thr221 in the N-terminus ankryn-4 (AR4) and linker (LH1) domains. Mutagenesis to alanine reveals T221 as a critical controller of resting TRPC6 conductance, and associated NFAT activity and pro-hypertrophic signaling. T→A mutations at sites homologous in closely related TRPC3 and TRPC7 also increases their activity. Molecular modeling predicts interactions between Thr221-

Indexed as

BiochemistryCell biologyCellular physiology

Identifiers

PMID36936781
PMCPMC10014292
OpenAlexW4323656864

What Socratic holds

Textfull text, public
LicenceCC BY
reference markers read4
measurements read73
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 Socratic graph.