Allosteric switching of Ca2+ permeability in the lysosomal ion channel TPC2 underpins biased agonist activation.

doi:10.1038/s44318-026-00882-1

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Article

Allosteric switching of Ca2+ permeability in the lysosomal ion channel TPC2 underpins biased agonist activation.

The EMBO journal - 1 Sept 2026

Mu Qianru, Saito Ryo, Ozola Franceska, Jaślan Dawid, Chu Pak Nin, Zaki Afroditi-Maria, Rubio-Alarcon Marcos, Keller Marco, Yuan Yu, Greig Alan, Silio Virginia, Bracher Franz, Biggin Philip C, Brailoiu Gabriela C, Brailoiu Eugen, Marchant Jonathan S, Grimm Christian, Lambie Eric J, Rahman Taufiq, Patel Sandip

Abstract excerpt

Ion channels possess selectivity filters that are hardwired to ensure the selective passage of ions. Lysosomal two-pore channels are unusual as they are able to switch their cation selectivity in an agonist-specific manner, allowing differential control of organellar activity. TPC2 is permeable to Ca2+ when activated by the calcium-mobilizing messenger NAADP, but largely Na+-selective when activated by the...

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Topics

Animals
Calcium
Lysosomes
Calcium Channels
Caenorhabditis elegans

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Two-Pore Channels

Humans

Allosteric Regulation

Permeability

NADP

Phosphatidylinositol Phosphates

Mutation

HEK293 Cells

Source

Open in PubMed Open full text

Identifiers

PMID: 42567924
DOI: 10.1038/s44318-026-00882-1
PMCID: PMC13578460

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