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Wnts control membrane potential in mammalian cancer cells

Ashmore, J; Olsen, H; Sørensen, N; Thrasivoulou, C; Ahmed, A; (2019) Wnts control membrane potential in mammalian cancer cells. The Journal of Physiology , 597 (24) pp. 5899-5914. 10.1113/jp278661. Green open access

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Abstract

The Wnt signalling network determines gene transcription with free intracellular Ca2+ (urn:x-wiley:00223751:media:tjp13863:tjp13863-math-0001) and β‐catenin as major intracellular signal transducers. Despite its critical importance during development and disease, many of the basic mechanisms of Wnt signal activation remain unclear. Here we show by single cell recording and simultaneous urn:x-wiley:00223751:media:tjp13863:tjp13863-math-0002 imaging in mammalian prostate cancer cells that an early step in the signal cascade is direct action on the cell membrane potential. We show that Wnt ligands 5A, 9B and 10B rapidly hyperpolarized the cells by activating K+ current by Ca2+ release from intracellular stores. Medium‐throughput multi‐well recordings showed responses to Wnts at concentrations of 2 nm. We identify a putative target for early events as a TRPM channel. Wnts thus act as ligands for ion channel activation in mammalian cells and membrane potential is an early indicator of control of transcription.

Type: Article
Title: Wnts control membrane potential in mammalian cancer cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/jp278661
Publisher version: https://doi.org/10.1113/jp278661
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10084333
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