Calcium signals at cytoneme contacts amplify Wnt/β-catenin signalling
- 1Living Systems Institute, University of Exeter, UK
Abstract
Wnt signalling controls morphogenesis, patterning and homeostasis across tissues. Because Wnt ligands are lipid-modified, their movement between cells cannot rely on simple diffusion and instead requires specialised transport mechanisms. Signalling filopodia, also known as cytonemes, have emerged as a key mediator of contact-dependent morphogen delivery. The mechanisms that stabilise signalling interfaces between Wnt ligand-bearing and receptor-bearing membranes at the cytoneme contact sites, a prerequisite for efficient Wnt ligand-receptor complex assembly and downstream pathway activation, remain poorly understood. Here, we show that HeLa cell cytonemes carry canonical Wnt components and form contact sites marked by focal Ca2+ transients. At these contacts, local Wnt and Ca2+ signals act in a positive feedback loop to promote longer-lasting interactions between neighbouring cells. Mechanistically, we find that E-cadherin/Cadherin 1 (CDH1) co-accumulates at these cytoneme contact sites in a Ca2+ - and Wnt-dependent manner, suggesting that contact stabilisation can be mediated by local adhesion. Consistent with this, presentation of Wnt ligands and CDH1 at cytoneme tips, together with Ca2+ availability, enhances Wnt signalosome formation at contact sites and, consequently, nuclear beta-catenin accumulation in the target cells. Our data support a model in which local Ca2+ transients stabilise cytoneme contacts and facilitate efficient Wnt ligand transfer to the receiving membrane, thereby enhancing canonical Wnt/beta-catenin signalling. We propose that focal Ca2+ signalling can serve as a contact-authentication step for morphogen signalling, converting transient cytoneme encounters into effective activators of the signal transduction cascade.
Related
- Compressive stress couples calcium signalling to translational control and proteostasis
- Calcium and autophagy connect photorespiratory oxidative signals with salicylic acid-mediated defense.
- Plant autoinhibited Ca2+-ATPases: shaping calcium signals for growth, stress adaptation, and crop improvement
- Clustered cytoneme interactions contribute to peripheral nervous system patterning in Drosophila
- ASC specks and α-synuclein amplify microglial NLRP3 inflammasome activation and co-localize with Lewy body pathology
BibTeX
@misc{cooper2026calcium,
title = {{Calcium signals at cytoneme contacts amplify Wnt/β-catenin signalling}},
author = {E. Cooper and C. Liddle and S. Scholpp},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751720},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751720v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Calcium signals at cytoneme contacts amplify Wnt/β-catenin signalling
AU - E. Cooper
AU - C. Liddle
AU - S. Scholpp
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751720
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751720v1
AB - Wnt signalling controls morphogenesis, patterning and homeostasis across tissues. Because Wnt ligands are lipid-modified, their movement between cells cannot rely on simple diffusion and instead requires specialised transport mechanisms. Signalling filopodia, also known as cytonemes, have emerged as a key mediator of contact-dependent morphogen delivery. The mechanisms that stabilise signalling interfaces between Wnt ligand-bearing and receptor-bearing membranes at the cytoneme contact sites, a prerequisite for efficient Wnt ligand-receptor complex assembly and downstream pathway activation, remain poorly understood. Here, we show that HeLa cell cytonemes carry canonical Wnt components and form contact sites marked by focal Ca2+ transients. At these contacts, local Wnt and Ca2+ signals act in a positive feedback loop to promote longer-lasting interactions between neighbouring cells. Mechanistically, we find that E-cadherin/Cadherin 1 (CDH1) co-accumulates at these cytoneme contact sites in a Ca2+ - and Wnt-dependent manner, suggesting that contact stabilisation can be mediated by local adhesion. Consistent with this, presentation of Wnt ligands and CDH1 at cytoneme tips, together with Ca2+ availability, enhances Wnt signalosome formation at contact sites and, consequently, nuclear beta-catenin accumulation in the target cells. Our data support a model in which local Ca2+ transients stabilise cytoneme contacts and facilitate efficient Wnt ligand transfer to the receiving membrane, thereby enhancing canonical Wnt/beta-catenin signalling. We propose that focal Ca2+ signalling can serve as a contact-authentication step for morphogen signalling, converting transient cytoneme encounters into effective activators of the signal transduction cascade.
ER -