Heterologous calcium-dependent inactivation of Orai1 by neighboring TRPV1 channels modulates cell migration and wound healing

Carlos Ernesto Bastián-Eugenio,Alicia Sampieri,Arlette Bohórquez-Hernández,Adán Guerrero,Jonathan Pacheco,Alberto Darszon,Luis Vaca,Alexander Asanov,Jose Pablo Ocelotl-Oviedo

doi:10.1038/s42003-019-0338-1

Carlos Ernesto Bastián-Eugenio, Alicia Sampieri + Show 7 more

Open Access

https://doi.org/10.1038/s42003-019-0338-1

Copy DOI

Abstract

Store-operated calcium entry (SOCE) is an essential calcium influx mechanism in animal cells. One of the most important auto regulatory control systems involves calcium-dependent inactivation (CDI) of the Orai channel, which prevents excessive calcium influx. In the present study we analyze the role of two channels in the induction of CDI on Orai1. Here we show that calcium entering through freely diffusing TRPV1 channels induce strong CDI on Orai1 while calcium entering through P2X4 channel does not. TRPV1 can induce CDI on Orai1 because both channels were found in close proximity in the cell membrane. This was not observed with P2X4 channels. To our knowledge, this is the first study demonstrating that calcium arising from different channels may contribute to the modulation of Orai1 through CDI in freely diffusing single channels of living cells. Our results highlight the role of TRPV1-mediated CDI on Orai1 in cell migration and wound healing.

Highlights

Store-operated calcium entry (SOCE) is an essential calcium influx mechanism in animal cells
The present study identifies the molecular determinants of the association between TRPV1 and Orai[1] channels, which favor heterologous calcium-dependent inactivation (CDI) of Orai[1] by calcium entering through single TRPV1 channels
Using super resolution studies on living cells, we observed that both channels move associated at the plasma membrane (PM)

Summary

Introduction

Store-operated calcium entry (SOCE) is an essential calcium influx mechanism in animal cells. TRPV1 can induce CDI on Orai[1] because both channels were found in close proximity in the cell membrane. This was not observed with P2X4 channels. To our knowledge, this is the first study demonstrating that calcium arising from different channels may contribute to the modulation of Orai[1] through CDI in freely diffusing single channels of living cells. Orai activity is regulated through a negative feedback mechanism that maintains intracellular Ca2+ homeostasis and prevents excessive Ca2+ influx. Such a mechanism is known as Ca2+-dependent inactivation (CDI). A single amino acid mutation alters FCDI in Orai[1] channels rendering the channel CDI insensitive[21]

Methods

Results

Conclusion