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How Many Orai's Does It Take to Make a CRAC Channel?

CRAC (Calcium Release-Activated Calcium) channels represent the primary pathway for so-called “store-operated calcium entry” – the cellular entry of calcium induced by depletion of intracellular calcium stores. These channels play a key role in diverse cellular activities, most noticeably in the dif...

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Detalles Bibliográficos
Autores principales: Thompson, Jill L., Shuttleworth, Trevor J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675454/
https://www.ncbi.nlm.nih.gov/pubmed/23743658
http://dx.doi.org/10.1038/srep01961
Descripción
Sumario:CRAC (Calcium Release-Activated Calcium) channels represent the primary pathway for so-called “store-operated calcium entry” – the cellular entry of calcium induced by depletion of intracellular calcium stores. These channels play a key role in diverse cellular activities, most noticeably in the differentiation and activation of Tcells, and in the response of mast cells to inflammatory signals. CRAC channels are formed by members of the recently discovered Orai protein family, with previous studies indicating that the functional channel is formed by a tetramer of Orai subunits. However, a recent report has shown that crystals obtained from the purified Drosophila Orai protein display a hexameric channel structure. Here, by comparing the biophysical properties of concatenated hexameric and tetrameric human Orai1 channels expressed in HEK293 cells, we show that the tetrameric channel displays the highly calcium-selective conductance properties consistent with endogenous CRAC channels, whilst the hexameric construct forms an essentially non-selective cation channel.