The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models
Ion channels are implicated in various diseases, including cancer, in which they modulate different aspects of cancer progression. In particular, potassium channels are often aberrantly expressed in cancers, a major example being provided by hERG1. The latter is generally complexed with β1 integrin...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Membranes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0375/12/11/1162 |
| _version_ | 1797464575080136704 |
|---|---|
| author | Ginevra Chioccioli Altadonna Alberto Montalbano Jessica Iorio Andrea Becchetti Annarosa Arcangeli Claudia Duranti |
| author_facet | Ginevra Chioccioli Altadonna Alberto Montalbano Jessica Iorio Andrea Becchetti Annarosa Arcangeli Claudia Duranti |
| author_sort | Ginevra Chioccioli Altadonna |
| collection | DOAJ |
| description | Ion channels are implicated in various diseases, including cancer, in which they modulate different aspects of cancer progression. In particular, potassium channels are often aberrantly expressed in cancers, a major example being provided by hERG1. The latter is generally complexed with β1 integrin in tumour cells, and such a molecular complex represents a new druggable hub. The present study focuses on the characterization of the functional consequences of the interaction between hERG1 and β1 integrins on different substrates over time. To this purpose, we studied the interplay alteration on the plasma membrane through patch clamp techniques in a cellular model consisting of human embryonic kidney (HEK) cells stably transfected with hERG1 and in a cancer cell model consisting of SH-SY5Y neuroblastoma cells, endogenously expressing the channel. Cells were seeded on different substrates known to stimulate β1 integrins, such as fibronectin (FN) for HEK-hERG1 and laminin (LMN) for SH-SY5Y. In HEK cells stably overexpressing hERG1, we observed a hERG1 current density increase accompanied by V<sub>rest</sub> hyperpolarization after cell seeding onto FN. Notably, a similar behaviour was shown by SH-SY5Y neuroblastoma cells plated onto LMN. Interestingly, we did not observe this phenomenon when plating the cells on substrates such as Bovine Serum Albumin (BSA) or Polylysine (PL), thus suggesting a crucial involvement of ECM proteins as well as of β1 integrin activation. |
| first_indexed | 2024-03-09T18:09:07Z |
| format | Article |
| id | doaj.art-a6bae20526424c3b8684769e3e0b4094 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-09T18:09:07Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-a6bae20526424c3b8684769e3e0b40942023-11-24T09:12:47ZengMDPI AGMembranes2077-03752022-11-011211116210.3390/membranes12111162The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell ModelsGinevra Chioccioli Altadonna0Alberto Montalbano1Jessica Iorio2Andrea Becchetti3Annarosa Arcangeli4Claudia Duranti5Department f Medical Biotechnologies, University of Siena, Strada delle Scotte, 53100 Siena, ItalyDepartment of Experimental and Clinical Medicine, University of Firenze, Viale G.B. Morgagni 50, 50134 Firenze, ItalyDepartment of Experimental and Clinical Medicine, University of Firenze, Viale G.B. Morgagni 50, 50134 Firenze, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Experimental and Clinical Medicine, University of Firenze, Viale G.B. Morgagni 50, 50134 Firenze, ItalyDepartment of Experimental and Clinical Medicine, University of Firenze, Viale G.B. Morgagni 50, 50134 Firenze, ItalyIon channels are implicated in various diseases, including cancer, in which they modulate different aspects of cancer progression. In particular, potassium channels are often aberrantly expressed in cancers, a major example being provided by hERG1. The latter is generally complexed with β1 integrin in tumour cells, and such a molecular complex represents a new druggable hub. The present study focuses on the characterization of the functional consequences of the interaction between hERG1 and β1 integrins on different substrates over time. To this purpose, we studied the interplay alteration on the plasma membrane through patch clamp techniques in a cellular model consisting of human embryonic kidney (HEK) cells stably transfected with hERG1 and in a cancer cell model consisting of SH-SY5Y neuroblastoma cells, endogenously expressing the channel. Cells were seeded on different substrates known to stimulate β1 integrins, such as fibronectin (FN) for HEK-hERG1 and laminin (LMN) for SH-SY5Y. In HEK cells stably overexpressing hERG1, we observed a hERG1 current density increase accompanied by V<sub>rest</sub> hyperpolarization after cell seeding onto FN. Notably, a similar behaviour was shown by SH-SY5Y neuroblastoma cells plated onto LMN. Interestingly, we did not observe this phenomenon when plating the cells on substrates such as Bovine Serum Albumin (BSA) or Polylysine (PL), thus suggesting a crucial involvement of ECM proteins as well as of β1 integrin activation.https://www.mdpi.com/2077-0375/12/11/1162hERG1adhesion moleculesion channelsfibronectinmacromolecular complexesECM proteins |
| spellingShingle | Ginevra Chioccioli Altadonna Alberto Montalbano Jessica Iorio Andrea Becchetti Annarosa Arcangeli Claudia Duranti The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models Membranes hERG1 adhesion molecules ion channels fibronectin macromolecular complexes ECM proteins |
| title | The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models |
| title_full | The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models |
| title_fullStr | The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models |
| title_full_unstemmed | The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models |
| title_short | The Interaction between hERG1 and β1 Integrins Modulates hERG1 Current in Different Pathological Cell Models |
| title_sort | interaction between herg1 and β1 integrins modulates herg1 current in different pathological cell models |
| topic | hERG1 adhesion molecules ion channels fibronectin macromolecular complexes ECM proteins |
| url | https://www.mdpi.com/2077-0375/12/11/1162 |
| work_keys_str_mv | AT ginevrachiocciolialtadonna theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT albertomontalbano theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT jessicaiorio theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT andreabecchetti theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT annarosaarcangeli theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT claudiaduranti theinteractionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT ginevrachiocciolialtadonna interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT albertomontalbano interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT jessicaiorio interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT andreabecchetti interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT annarosaarcangeli interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels AT claudiaduranti interactionbetweenherg1andb1integrinsmodulatesherg1currentindifferentpathologicalcellmodels |