1. CRACM1, CRACM2, and CRACM3 Are Store-Operated Ca2+ Channels with Distinct Functional Properties
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Lis, Annette, Peinelt, Christine, Beck, Andreas, Parvez, Suhel, Monteilh-Zoller, Mahealani, Fleig, Andrea, and Penner, Reinhold
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PROTEINS , *CELL membranes , *BIOLOGICAL membranes , *BACTERIAL cell walls - Abstract
Summary: STIM1 in the endoplasmic reticulum and CRACM1 in the plasma membrane are essential molecular components for controlling the store-operated CRAC current . CRACM1 proteins multimerize and bind STIM1 , and the combined overexpression of STIM1 and CRACM1 reconstitutes amplified CRAC currents . Mutations in CRACM1 determine the selectivity of CRAC currents, demonstrating that CRACM1 forms the CRAC channel''s ion-selective pore , but the CRACM1 homologs CRACM2 and CRACM3 are less well characterized . Here, we show that both CRACM2 and CRACM3, when overexpressed in HEK293 cells stably expressing STIM1, potentiate ICRAC to current amplitudes 15–20 times larger than native ICRAC. A nonconducting mutation of CRACM1 (E106Q) acts as a dominant negative for all three CRACM homologs, suggesting that they can form heteromultimeric channel complexes. All three CRACM homologs exhibit distinct properties in terms of selectivity for Ca2+ and Na+, differential pharmacological effects in response to 2-APB, and strikingly different feedback regulation by intracellular Ca2+. Each of the CRAC channel proteins'' specific functional features and the potential heteromerization provide for flexibility in shaping Ca2+ signals, and their characteristic biophysical and pharmacological properties will aid in identifying CRAC-channel species in native cells that express them. [Copyright &y& Elsevier]
- Published
- 2007
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