Calmodulin regulation of the calcium-leak channel Sec61 is unique to vertebrates

Autor(en): Harsman, Anke
Kopp, Annika
Wagner, Richard 
Zimmermann, Richard
Jung, Martin 
Stichwörter: Biochemistry & Molecular Biology; calcium homeostasis; endoplasmic reticulum; ER calcium leakage; PROTEIN; Sec61 complex; YEAST CALMODULIN; yeast Saccharomyces cerevisiae
Erscheinungsdatum: 2011
Volumen: 5
Ausgabe: 4
Startseite: 293
Seitenende: 298
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 Sec61 alpha from Canis familiaris that binds CaM, but not Ca2+-free apo-CaM, with nanomolar affinity and sequence specificity. In single channel lipid bilayer measurements, CaM potently mediated Sec61-channel closure in a Ca2+-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 Ca2+. Therefore, CaM binding to the cytosolic N-terminus of Sec61a is involved in limiting Ca2+-leakage from the ER in C. familiaris but not S. cerevisiae.
ISSN: 19336950
DOI: 10.4161/chan.5.4.16160

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