Calcium Currents Are Enhanced by α2δ-1 Lacking Its Membrane Anchor*

نویسندگان

  • Ivan Kadurin
  • Anita Alvarez-Laviada
  • Shu Fun Josephine Ng
  • Ryan Walker-Gray
  • Marianna D'Arco
  • Michael G. Fadel
  • Wendy S. Pratt
  • Annette C. Dolphin
چکیده

The accessory α(2)δ subunits of voltage-gated calcium channels are membrane-anchored proteins, which are highly glycosylated, possess multiple disulfide bonds, and are post-translationally cleaved into α(2) and δ. All α(2)δ subunits have a C-terminal hydrophobic, potentially trans-membrane domain and were described as type I transmembrane proteins, but we found evidence that they can be glycosylphosphatidylinositol-anchored. To probe further the function of membrane anchoring in α(2)δ subunits, we have now examined the properties of α(2)δ-1 constructs truncated at their putative glycosylphosphatidylinositol anchor site, located before the C-terminal hydrophobic domain (α(2)δ-1ΔC-term). We find that the majority of α(2)δ-1ΔC-term is soluble and secreted into the medium, but unexpectedly, some of the protein remains associated with detergent-resistant membranes, also termed lipid rafts, and is extrinsically bound to the plasma membrane. Furthermore, heterologous co-expression of α(2)δ-1ΔC-term with Ca(V)2.1/β1b results in a substantial enhancement of the calcium channel currents, albeit less than that produced by wild-type α(2)δ-1. These results call into question the role of membrane anchoring of α(2)δ subunits for calcium current enhancement.

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عنوان ژورنال:

دوره 287  شماره 

صفحات  -

تاریخ انتشار 2012