کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1944903 1053244 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of glycine residues highly conserved in the S2–S3 linkers of domains I and II of voltage-gated calcium channel α1 subunits
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Role of glycine residues highly conserved in the S2–S3 linkers of domains I and II of voltage-gated calcium channel α1 subunits
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1798, Issue 5, May 2010, Pages 966–974
نویسندگان
, , , , , , ,