PhD Scientific Days 2026

Poster Session 1.A - Molecular Medicine

The role of PMCA4B in the regulation of collective cell migration via an SNX27-mediated recycling pathway

Name of the presenter

Nagy, Réka

Institute/workplace of the presenter

SE, Department of Transfusion Medicine

Authors

Réka Nagy¹, Rita Padányi², Lívia Ambrus³, Boglárka Zámbó⁴, Gergő Gógl⁴, Tamás Hegedűs², Ágnes Enyedi³, Sarolta Tóth³
1: Semmelweis University, Department of Transfusion Medicine, Budapest; Semmelweis University, Doctoral Collage, Budapest
2: Semmelweis University, Institute of Biophysics and Radiation Biology, Budapest
3: Semmelweis University, Department of Transfusion Medicine, Budapest
4: Université Côte d’Azur, Institut de Biologie Valrose (iBV), Nice

Text of the abstract

Introduction: Collective migration of epithelial cells plays a crucial role in wound healing and tissue regeneration, processes closely linked to cell polarization. Maintenance of local Ca2+ levels is essential for regulating cytoskeletal dynamics.
Aims: We aimed to investigate the role of the plasma membrane calcium ATPase 4b isoform (PMCA4b) in collective cell migration and to characterize its intracellular trafficking and regulatory mechanisms.
Methods: Collective migration was studied using wound healing assays in human MCF-7 epithelial breast cancer cells. PMCA4 expression was modulated by overexpression and silencing approaches. Individual cell movement was analyzed to assess coordination and directionality. Protein interactions and trafficking were examined using native holdup assays and colocalization studies in MCF-7 and HEK293 cells.
Results: PMCA4b-expressing MCF-7 cells exhibited faster wound closure compared to parental cells, whereas silencing of PMCA4 significantly impaired migration coordination. Analysis of individual cell trajectories revealed that PMCA4b expression resulted in more linear and directed movement, leading to more efficient collective migration. In contrast to parental cells, where coordinated movement was largely restricted to cells at the wound edge, this directed migration in PMCA4b-expressing cells was also evident in inner cell layers. We demonstrated that PMCA4b can bind directly to the endosomal sorting regulator SNX27. In HEK293 cells, strong colocalization of PMCA4b, SNX27, and F-actin was observed in cellular protrusions at the periphery of cell clusters. Similarly, in MCF-7 cells, triple colocalization was detected at the leading edge of cells facing the wound.
Conclusion: Our results demonstrate that SNX27-dependent recycling of PMCA4b contributes to the maintenance of local Ca2+ homeostasis, thereby regulating cell polarization and coordinated collective migration of epithelial cells.
Funding: 2024-1.2.3-HU-RIZONT-2024-00003; TKP2021-EGA-24; 2025-2.1.1-EKÖP-2025-00014 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.