Role of glycine residues highly conserved in the S2-S3 linkers of domains I and II of voltage-gated calcium channel α1 subunits

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Abstract

The pore-forming component of voltage-gated calcium channels, α1 subunit, contains four structurally conserved domains (I-IV), each of which contains six transmembrane segments (S1-S6). We have shown previously that a Gly residue in the S2-S3 linker of domain III is completely conserved from yeasts to humans and important for channel activity. The Gly residues in the S2-S3 linkers of domains I and II, which correspond positionally to the Gly in the S2-S3 linker of domain III, are also highly conserved. Here, we investigated the role of the Gly residues in the S2-S3 linkers of domains I and II of Cav1.2. Each of the Gly residues was replaced with Glu or Gln to produce mutant Cav1.2s; G182E, G182Q, G579E, G579Q, and the resulting mutants were transfected into BHK6 cells. Whole-cell patch-clamp recordings showed that current-voltage relationships of the four mutants were the same as those of wild-type Cav1.2. However, G182E and G182Q showed significantly smaller current densities because of mislocalization of the mutant proteins, suggesting that Gly182 in domain I is involved in the membrane trafficking or surface expression of α1 subunit. On the other hand, G579E showed a slower voltage-dependent current inactivation (VDI) compared to Cav1.2, although G579Q showed a normal VDI, implying that Gly579 in domain II is involved in the regulation of VDI and that the incorporation of a negative charge alters the VDI kinetics. Our findings indicate that the two conserved Gly residues are important for α1 subunit to become functional. © 2010 Elsevier B.V. All rights reserved.

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Teng, J., Iida, K., Ito, M., Izumi-Nakaseko, H., Kojima, I., Adachi-Akahane, S., & Iida, H. (2010). Role of glycine residues highly conserved in the S2-S3 linkers of domains I and II of voltage-gated calcium channel α1 subunits. Biochimica et Biophysica Acta - Biomembranes, 1798(5), 966–974. https://doi.org/10.1016/j.bbamem.2010.01.004

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