Domain assembly of NAADP-gated two-pore channels.

ABSTRACT: TPCs (two-pore channels) have recently been identified as targets for the Ca2+-mobilizing messenger NAADP (nicotinic acid-adenine dinucleotide phosphate). TPCs have a unique structure consisting of cytosolic termini, two hydrophobic domains (I and II) each comprising six transmembrane regions and a pore, and a connecting cytosolic loop; however, little is known concerning how these channels are assembled. In the present paper, we report that both domain I and II of human TPCs are capable of independent insertion into membranes, whereas the loop linking the domains fails to insert. Pairs of transmembrane regions within domain I of TPC1 are also capable of insertion, consistent with sequential translational integration of hydrophobic regions. Insertion of the first two transmembrane regions,

SUBMITTER: Churamani D 

PROVIDER: S-EPMC3242506 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature