Interaction of calmodulin with Sec61 alpha limits Ca2+ leakage from the endoplasmic reticulum
Autor(en): | Erdmann, Frank Schaeuble, Nico Lang, Sven Jung, Martin Honigmann, Alf Ahmad, Mazen Dudek, Johanna Benedix, Julia Harsman, Anke Kopp, Annika Helms, Volkhard Cavalie, Adolfo Wagner, Richard Zimmermann, Richard |
Stichwörter: | Biochemistry & Molecular Biology; BOUND RIBOSOMES; CALCIUM LEAK; calmodulin; Cell Biology; COMPLEX; endoplasmic reticulum; ER calcium leakage; ER MEMBRANE; INOSITOL 1,4,5-TRISPHOSPHATE; INTRACELLULAR CA2+; IQ motif; PROTEIN-CONDUCTING CHANNEL; RELEASE CHANNEL; RYANODINE RECEPTOR; Sec61 complex; TRANSLOCON | Erscheinungsdatum: | 2011 | Herausgeber: | WILEY | Enthalten in: | EMBO JOURNAL | Band: | 30 | Ausgabe: | 1 | Startseite: | 17 | Seitenende: | 31 | Zusammenfassung: | 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, as formed by Sec61 complexes in the ER membrane, would seriously interfere with the regulated release of calcium from the ER lumen into the cytosol, an essential mechanism for intracellular signalling. We identified a calmodulin (CaM)-binding motif in the cytosolic N-terminus of mammalian Sec61 alpha that bound CaM but not Ca2+-free apocalmodulin with nanomolar affinity and sequence specificity. In single-channel measurements, CaM potently mediated Sec61-channel closure in Ca2+-dependent manner. At the cellular level, two different CaM antagonists stimulated calcium release from the ER through Sec61 channels. However, protein transport into microsomes was not modulated by Ca2+-CaM. Molecular modelling of the ribosome/Sec61/CaM complexes supports the view that simultaneous ribosome and CaM binding to the Sec61 complex may be possible. Overall, CaM is involved in limiting Ca2+ leakage from the ER. The EMBO Journal (2011) 30, 17-31. doi:10.1038/emboj.2010.284; Published online 23 November 2010 |
ISSN: | 02614189 | DOI: | 10.1038/emboj.2010.284 |
Zur Langanzeige
Seitenaufrufe
3
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 06.06.2024