title: Calmodulin regulation of the calcium-leak channel Sec61 is unique to vertebrates.
abstract: In eukaryotes, protein transport into the endoplasmic reticulum (ER) is facilitated by a protein-conducting channel, the Sec61 complex. The presence of large, water-filled pores with uncontrolled ion permeability, such as those formed by Sec61 complexes in the ER membrane, would interfere with the regulated release of calcium from the ER lumen into the cytosol, an essential mechanism of intracellular signaling. We identified a calmodulin (CaM) binding motif in the cytosolic N-terminus of Sec61α from Canis familiaris that binds CaM, but not Ca(2+)-free apo-CaM, with nanomolar affinity and sequence specificity. In single channel lipid bilayer measurements, CaM potently mediated Sec61-channel closure in a Ca(2+)-dependent manner. No functional CaM binding motif was identified in the corresponding region of Sec61p from Saccharomyces cerevisiae, and no channel closure occurred in the presence of CaM and Ca(2+). Therefore, CaM binding to the cytosolic N-terminus of Sec61α is involved in limiting Ca(2+)-leakage from the ER in C. familiaris but not S. cerevisiae.
authors.affiliation: Osnabrück University, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Harsman
authors.forename: Annika
authors.initials: A
authors.lastname: Kopp
authors.forename: Richard
authors.initials: R
authors.lastname: Wagner
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000069816:SEC Translocation Channels; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002118:Calcium