Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins

AUTOR(ES)

Scrimgeour, N

FONTE

Blackwell Science Inc

RESUMO

Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca2+ release activated Ca2+ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca2+ sensor required for activation of CRAC current (ICRAC) by store depletion. It is not known, however, if the role of STIM1 is limited exclusively to Ca2+ sensing, or whether interaction between Orai1 and STIM1, either direct or indirect, also defines the properties of ICRAC. In this study we investigated how the relative expression levels of ectopic Orai1 and STIM1 affect the properties of ICRAC. The results show that cells expressing low Orai1 : STIM1 ratios produce ICRAC with strong fast Ca2+-dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce ICRAC with strong activation at negative potentials. Moreover, the expression ratio of Orai1 and STIM1 affects Ca2+, Ba2+ and Sr2+ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca2+ channels formed by Orai1 depend on its interaction with STIM1, and that the stoichiometry of this interaction may vary depending on the relative expression levels of these proteins.

Documentos Relacionados

• STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg
• TRPC channels function independently of STIM1 and Orai1
• Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration
• The Short N-terminal Domains of STIM1 and STIM2 Control the Activation Kinetics of Orai1 Channels*
• Calmodulin regulation of light adaptation and store-operated dark current in Drosophila photoreceptors