A synthetic method to assay polycystin channel biophysics.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
28 Oct 2024
Historique:
medline: 28 10 2024
pubmed: 28 10 2024
entrez: 28 10 2024
Statut: epublish

Résumé

Ion channels are biological transistors that control ionic flux across cell membranes to regulate electrical transmission and signal transduction. They are found in all biological membranes and their conductive state kinetics are frequently disrupted in human diseases. Organelle ion channels are among the most resistant to functional and pharmacological interrogation. Traditional channel protein reconstitution methods rely upon exogenous expression and/or purification from endogenous cellular sources which are frequently contaminated by resident ionophores. Here, we describe a fully synthetic method to assay functional properties of polycystin channels that natively traffic to primary cilia and endoplasmic reticulum organelles. Using this method, we characterize their oligomeric assembly, membrane integration, orientation, and conductance while comparing these results to their endogenous channel properties. Outcomes define a novel synthetic approach that can be applied broadly to investigate channels resistant to biophysical analysis and pharmacological characterization.

Identifiants

pubmed: 39466685
doi: 10.7554/eLife.98534
pii: 98534
doi:
pii:

Substances chimiques

TRPP Cation Channels 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIH HHS
ID : T32 GM008382
Pays : United States
Organisme : NIH HHS
ID : U2CDK129917
Pays : United States
Organisme : NIH HHS
ID : TL1DK132769
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32DK137477-01A1
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123463-01
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131118-01
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2024, Larmore et al.

Déclaration de conflit d'intérêts

ML, OE, NK, PD No competing interests declared

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Auteurs

Megan Larmore (M)

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, United States.

Orhi Esarte Palomero (O)

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, United States.

Neha Kamat (N)

Department of Biomedical Engineering, McCormick School of Engineering and Applied Science, Northwestern University, Evanston, United States.
Center for Synthetic Biology, Northwestern University, Evanston, United States.

Paul G DeCaen (PG)

Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, United States.
Chemistry of Life Processes Institute, Northwestern University, Evanston, United States.

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