KCNQ1 disruption alters human neuronal development through mitochondrial and insulin signalling pathways
Abstract
KCNQ1 encodes a voltage-gated potassium channel implicated in peripheral and neurological disorders, but its role in human neurodevelopment remains unclear. We generated KCNQ1 knockout (KO) human induced pluripotent stem cells and differentiated them into neural stem cells (NSCs) and cortical neurons. KCNQ1 -deficient NSCs show impaired neurite outgrowth, linked to reduced cell adhesion and disrupted neural cell adhesion molecule signalling, a phenotype reproduced by pharmacological KCNQ1 inhibition. Multi-omics and follow-up analyses reveal mitochondrial dysfunction, including reduced mitochondrial copy number and ATP synthase expression. KO cells also show impaired insulin signalling, with diminished insulin receptor gene expression and altered RAS-MAPK and PI3K-AKT pathways. In differentiated neuronal cultures, KCNQ1 loss decreases synaptic activity and maintains an immature transcriptional profile. Together, these findings identify a role for KCNQ1 in regulating cell adhesion, mitochondrial function, insulin signalling, and neuronal maturation, expanding our understanding of processes that may contribute to neurological manifestations associated with KCNQ1 -related disorders.
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BibTeX
@article{schall2026kcnq1,
title = {{KCNQ1 disruption alters human neuronal development through mitochondrial and insulin signalling pathways}},
author = {Dorothea Schall and Baran E. Güler and Siamand Alibrahim and Mahmudul Hasan and Naeem Ahmad and Joanna Widomska and Claudio Acuna and Mairéad Sullivan and Ralph Röth and Chang Liu and Linda Blaier and Katalin Vincze and Karin Burau and Simone Macri and Daniela Mauceri and Marcin Luzarowski and Ágota Apáti and János M. Réthelyi and Geert Poelmans and Gudrun A. Rappold and Barbara Franke and Jeffrey C. Glennon and Simone Berkel},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11111-0},
url = {https://www.nature.com/articles/s42003-026-11111-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - KCNQ1 disruption alters human neuronal development through mitochondrial and insulin signalling pathways
AU - Dorothea Schall
AU - Baran E. Güler
AU - Siamand Alibrahim
AU - Mahmudul Hasan
AU - Naeem Ahmad
AU - Joanna Widomska
AU - Claudio Acuna
AU - Mairéad Sullivan
AU - Ralph Röth
AU - Chang Liu
AU - Linda Blaier
AU - Katalin Vincze
AU - Karin Burau
AU - Simone Macri
AU - Daniela Mauceri
AU - Marcin Luzarowski
AU - Ágota Apáti
AU - János M. Réthelyi
AU - Geert Poelmans
AU - Gudrun A. Rappold
AU - Barbara Franke
AU - Jeffrey C. Glennon
AU - Simone Berkel
PY - 2026
DA - 2026/10/13
JO - Communications Biology
DO - 10.1038/s42003-026-11111-0
UR - https://www.nature.com/articles/s42003-026-11111-0
AB - KCNQ1 encodes a voltage-gated potassium channel implicated in peripheral and neurological disorders, but its role in human neurodevelopment remains unclear. We generated KCNQ1 knockout (KO) human induced pluripotent stem cells and differentiated them into neural stem cells (NSCs) and cortical neurons. KCNQ1 -deficient NSCs show impaired neurite outgrowth, linked to reduced cell adhesion and disrupted neural cell adhesion molecule signalling, a phenotype reproduced by pharmacological KCNQ1 inhibition. Multi-omics and follow-up analyses reveal mitochondrial dysfunction, including reduced mitochondrial copy number and ATP synthase expression. KO cells also show impaired insulin signalling, with diminished insulin receptor gene expression and altered RAS-MAPK and PI3K-AKT pathways. In differentiated neuronal cultures, KCNQ1 loss decreases synaptic activity and maintains an immature transcriptional profile. Together, these findings identify a role for KCNQ1 in regulating cell adhesion, mitochondrial function, insulin signalling, and neuronal maturation, expanding our understanding of processes that may contribute to neurological manifestations associated with KCNQ1 -related disorders.
SN - 2399-3642
ER -