Evidence map›Paper›PMID 41353348›Full record

ArticleNature communications2025

Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.

Arden Darko-Boateng, Emmanuel Afriyie, Travis J Morgenstern, Sri Karthika Shanmugam, Xinle Zou, Yianni D Laloudakis, Papiya Choudhury, Meera Desai, Robert S Kass, Francesca Vallese and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Arden Darko-Boateng *Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5298-0755
Emmanuel Afriyie *Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0009-0007-1073-2765
Travis J Morgenstern *Department of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, NY, USA.
Sri Karthika ShanmugamDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-1467-401X
Xinle ZouDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, NY, USA.
Yianni D LaloudakisVagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Papiya ChoudhuryDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.
Meera DesaiDuke University, Durham, NC, USA.
Robert S KassDepartment of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, NY, USA.
Francesca ValleseDepartment of Chemistry and Biochemistry, The City University of New York, New York, NY, USA.
Oliver B ClarkeDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA. oc2188@cumc.columbia.edu.ORCID http://orcid.org/0000-0003-1876-196X
Henry M ColecraftDepartment of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY, USA. hc2405@cumc.columbia.edu.ORCID http://orcid.org/0000-0002-2340-8899

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Structure-Function of Calcium Channel Complexes in Cardiac Physiology and DiseaseP01HL164319 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREW Robert MARKS · 2023 to 2026
$12.1M
L-type channel trafficking and modulation in heartR01HL121253 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Henry M. Colecraft, Steven O Marx · 2014 to 2026
$8.4M
Towards Novel Therapies for CACNA1A Neurological DisordersR01NS126850 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Henry M. Colecraft · 2022 to 2026
$2.7M
Ubiquitin Regulation of K Channels in Health and DiseaseR01HL142111 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI COLECRAFT, HENRY M. · 2018 to 2021
$2.3M
Novel genetically-encoded inhibitors to probe functional logic of Cav-beta molecular diversityR21NS130409 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI COLECRAFT, HENRY M. · 2022 to 2022
$450k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
Engineering Nanobodies To Study Beta Subunit-Specific Voltage-Gated Calcium Channel Complexes in Pancreatic Beta CellsF31DK118866 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MORGENSTERN, TRAVIS JAMES · 2018 to 2020
$135k
American Heart Association (American Heart Association, Inc.) 20PRE35210815American Heart Association (American Heart Association, Inc.) POST1019343NCI NIH HHS P30 CA013696NCRR NIH HHS S10 RR027050NHLBI NIH HHS P01 HL164319NHLBI NIH HHS R01 HL121253NHLBI NIH HHS R01 HL142111NIDDK NIH HHS F31 DK118866NINDS NIH HHS R01 NS126850NINDS NIH HHS R21 NS130409U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) P01-HL164319U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) RO1-HL121253U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) RO1-HL142111U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01-NS126850U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R21-NS130409
6 · The paper itself

Abstract

Targeted protein degradation/downregulation (TPD/TPDR) is a disruptive paradigm for developing therapeutics. <2% of ~600 E3 ligases have been exploited for this modality, and efficacy for multi-subunit ion channels has not been demonstrated. NEDD4-2 E3 ligase regulates myriad ion channels, but its utility for TPD/TPDR is uncertain due to complex regulatory mechanisms. Here, we identify a nanobody that binds NEDD4-2 HECT domain without disrupting catalysis sites as revealed by cryo-electron microscopy and in vitro ubiquitination assays. Recruiting NEDD4-2 to diverse ion channels (Ca

Indexed as

Ion ChannelsNedd4 Ubiquitin Protein LigasesSingle-Domain AntibodiesAnimalsCryoelectron MicroscopyEpithelial Sodium ChannelsHEK293 CellsHumansKCNQ1 Potassium ChannelProtein BindingUbiquitinationEpithelial Sodium ChannelsIon ChannelsKCNQ1 Potassium ChannelNedd4L protein, humanNedd4 protein, humanNedd4 Ubiquitin Protein LigasesSingle-Domain Antibodies

Identifiers

PMID41353348
PMCPMC12796476

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.