β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane
The interactions between TRPV1 and µ-opioid receptors (MOR) have recently attracted much attention because these two receptors play important roles in pain pathways and can apparently modulate each other’s functioning. However, the knowledge about signaling interactions and crosstalk between these t...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/13/4626 |
| _version_ | 1797563809183825920 |
|---|---|
| author | Barbora Melkes Vendula Markova Lucie Hejnova Jiri Novotny |
| author_facet | Barbora Melkes Vendula Markova Lucie Hejnova Jiri Novotny |
| author_sort | Barbora Melkes |
| collection | DOAJ |
| description | The interactions between TRPV1 and µ-opioid receptors (MOR) have recently attracted much attention because these two receptors play important roles in pain pathways and can apparently modulate each other’s functioning. However, the knowledge about signaling interactions and crosstalk between these two receptors is still limited. In this study, we investigated the mutual interactions between MOR and TRPV1 shortly after their activation in HEK293 cells expressing these two receptors. After activation of one receptor we observed significant changes in the other receptor’s lateral mobility and vice versa. However, the changes in receptor movement within the plasma membrane were not connected with activation of the other receptor. We also observed that plasma membrane β-arrestin 2 levels were altered after treatment with agonists of both these receptors. Knockdown of β-arrestin 2 blocked all changes in the lateral mobility of both receptors. Furthermore, we found that β-arrestin 2 can play an important role in modulating the effectiveness of ERK1/2 phosphorylation after activation of MOR in the presence of TRPV1. These data suggest that β-arrestin 2 and ERK1/2 are important mediators between these two receptors and their signaling pathways. Collectively, MOR and TRPV1 can mutually affect each other’s behavior and β-arrestin 2 apparently plays a key role in the bidirectional crosstalk between these two receptors in the plasma membrane. |
| first_indexed | 2024-03-10T18:48:25Z |
| format | Article |
| id | doaj.art-6eb887a153924badb024e6007b0d25a9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:48:25Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6eb887a153924badb024e6007b0d25a92023-11-20T05:19:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012113462610.3390/ijms21134626β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma MembraneBarbora Melkes0Vendula Markova1Lucie Hejnova2Jiri Novotny3Department of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 128 00 Prague, Czech RepublicThe interactions between TRPV1 and µ-opioid receptors (MOR) have recently attracted much attention because these two receptors play important roles in pain pathways and can apparently modulate each other’s functioning. However, the knowledge about signaling interactions and crosstalk between these two receptors is still limited. In this study, we investigated the mutual interactions between MOR and TRPV1 shortly after their activation in HEK293 cells expressing these two receptors. After activation of one receptor we observed significant changes in the other receptor’s lateral mobility and vice versa. However, the changes in receptor movement within the plasma membrane were not connected with activation of the other receptor. We also observed that plasma membrane β-arrestin 2 levels were altered after treatment with agonists of both these receptors. Knockdown of β-arrestin 2 blocked all changes in the lateral mobility of both receptors. Furthermore, we found that β-arrestin 2 can play an important role in modulating the effectiveness of ERK1/2 phosphorylation after activation of MOR in the presence of TRPV1. These data suggest that β-arrestin 2 and ERK1/2 are important mediators between these two receptors and their signaling pathways. Collectively, MOR and TRPV1 can mutually affect each other’s behavior and β-arrestin 2 apparently plays a key role in the bidirectional crosstalk between these two receptors in the plasma membrane.https://www.mdpi.com/1422-0067/21/13/4626μ-opioid receptorTRPV1β-arrestin 2ERK1/2biased signalingreceptor lateral mobility |
| spellingShingle | Barbora Melkes Vendula Markova Lucie Hejnova Jiri Novotny β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane International Journal of Molecular Sciences μ-opioid receptor TRPV1 β-arrestin 2 ERK1/2 biased signaling receptor lateral mobility |
| title | β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane |
| title_full | β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane |
| title_fullStr | β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane |
| title_full_unstemmed | β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane |
| title_short | β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane |
| title_sort | β arrestin 2 and erk1 2 are important mediators engaged in close cooperation between trpv1 and µ opioid receptors in the plasma membrane |
| topic | μ-opioid receptor TRPV1 β-arrestin 2 ERK1/2 biased signaling receptor lateral mobility |
| url | https://www.mdpi.com/1422-0067/21/13/4626 |
| work_keys_str_mv | AT barboramelkes barrestin2anderk12areimportantmediatorsengagedinclosecooperationbetweentrpv1andμopioidreceptorsintheplasmamembrane AT vendulamarkova barrestin2anderk12areimportantmediatorsengagedinclosecooperationbetweentrpv1andμopioidreceptorsintheplasmamembrane AT luciehejnova barrestin2anderk12areimportantmediatorsengagedinclosecooperationbetweentrpv1andμopioidreceptorsintheplasmamembrane AT jirinovotny barrestin2anderk12areimportantmediatorsengagedinclosecooperationbetweentrpv1andμopioidreceptorsintheplasmamembrane |