NDLI: The Third Transmembrane Segment of Orai1 Protein Modulates Ca2+ Release-activated Ca2+ (CRAC) Channel Gating and Permeation Properties*

Content Provider	PubMed Central
Author	Srikanth, Sonal Yee, Ma-khin Win Gwack, Yousang Bernard, Ribalet
Copyright Year	2011
Abstract	Orai1, the pore subunit of Ca2+ release-activated Ca2+ channels, has four transmembrane segments (TMs). The first segment, TMI, lines the pore and plays an important role in channel activation and ion permeation. TMIII, on the other hand, does not line the pore but still regulates channel gating and permeation properties. To understand the role of TMIII, we have mutated and characterized several residues in this domain. Mutation of Trp-176 to Cys (W176C) and Gly-183 to Ala (G183A) had dramatic effects. Unlike wild-type channels, which exhibit little outward current and are activated by STIM1, W176C mutant channels exhibited a large outward current at positive potentials and were constitutively active in the absence of STIM1. G183A mutant channels also exhibited substantial outward currents but were active only in the presence of 2-aminoethoxydiphenyl borate (2-APB), irrespective of STIM1. With W176C mutant channels inward, monovalent currents were blocked by Ca2+ with a high affinity similar to the wild type, but the Ca2+-dependent blocking of outward currents differed in the two cases. Although a 50% block of the WT outward current required 250 μm Ca2+, more than 6 mm was necessary to have the same effect on W176C mutant channels. In the presence of extracellular Ca2+, W176C and G183A outward currents developed slowly in a voltage-dependent manner, whereas they developed almost instantaneously in the absence of Ca2+. These changes in permeation and gating properties mimic the changes induced by mutations of Glu-190 in TMIII and Asp-110/Asp-112 in the TMI/TMII loop. On the basis of these data, we propose that TMIII maintains negatively charged residues at or near the selectivity filter in a conformation that facilitates Ca2+ inward currents and prevents outward currents of monovalent cations. In addition, to controlling selectivity, TMIII may also stabilize channel gating in a closed state in the absence of STIM1 in a Trp-176-dependent manner.
Related Links	http://dx.doi.org/10.1074/jbc.m111.265884
Ending Page	35328
Page Count	11
Starting Page	35318
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	40
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-10-07
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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The Third Transmembrane Segment of Orai1 Protein Modulates Ca2+ Release-activated Ca2+ (CRAC) Channel Gating and Permeation Properties

Differential Roles of the C and N Termini of Orai1 Protein in Interacting with Stromal Interaction Molecule 1 (STIM1) for Ca2+ Release-activated Ca2+ (CRAC) Channel Activation

Voltage Gating at the Selectivity Filter of the Ca2+ Release-activated Ca2+ Channel Induced by Mutation of the Orai1 Protein*

Differential Roles of the C and N Termini of Orai1 Protein in Interacting with Stromal Interaction Molecule 1 (STIM1) for Ca2+ Release-activated Ca2+ (CRAC) Channel Activation*

A Ca2+ Release-activated Ca2+ (CRAC) Modulatory Domain (CMD) within STIM1 Mediates Fast Ca2+-dependent Inactivation of ORAI1 Channels* ♦

Voltage Gating at the Selectivity Filter of the Ca2+ Release-activated Ca2+ Channel Induced by Mutation of the Orai1 Protein

A CRAC Reporter♦ A Ca2+ Release-activated Ca2+ (CRAC) Modulatory Domain (CMD) within STIM1 Mediates Fast Ca2+-dependent Inactivation of ORAI1 Channels

Authentic CRAC channel activity requires STIM1 and the conserved portion of the Orai N terminus

Understanding How Components of a Ca2+ Release-activated Ca2+ Channel Function♦ The Extended Transmembrane Orai1 N-terminal (ETON) Region Combines Binding Interface and Gate for Orai1 Activation by STIM1

The Third Transmembrane Segment of Orai1 Protein Modulates Ca2+ Release-activated Ca2+ (CRAC) Channel Gating and Permeation Properties*

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