Ribosome-translocon complex mediates calcium leakage from endoplasmic reticulum stores.Report as inadecuate




Ribosome-translocon complex mediates calcium leakage from endoplasmic reticulum stores. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la psysiopathologie de la prostate 2 School of Cellular and Molecular Biosciences

Abstract : Under resting conditions, the endoplasmic reticulum ER intraluminal free calcium concentration Ca2+ER reflects a balance between active uptake by Ca2+-ATPases and passive efflux via -leak channels-. Despite their physiological importance and ubiquitous leak pathway mechanism, very little is known about the molecular nature of these channels. As it has been suggested that the open translocon pore complex of the ER is permeable to ions and neutral molecules, we hypothesized that the ribosome-bound translocon would be permeable to calcium after treatment with puromycin, a translation inhibitor that specifically releases polypeptide chains. At this time, the translocon channel is left open. We measured the fluctuations in cytoplasmic and luminal calcium concentrations using fluorescent dyes fura-2 and magfura-2, respectively. The calcium release induced by thapsigargin a Ca2+-ATPase inhibitor was lower after puromycin treatment. Puromycin also reduced the Ca2+ER level when perfused into the medium, but was ineffective after anisomycin pre-treatment an inhibitor of the peptidyl transferase. Puromycin had a similar effect in the presence of heparin and ryanodine. This puromycin-evoked Ca2+ER decrease was specific to the translocon. We conclude that the translocon complex is a major calcium leak channel. This work reveals a new role for the translocon which is involved in the control of the Ca2+ER and could therefore supervise many physiological processes, including gene expression and apoptosis.





Author: Fabien Van Coppenolle - Fabien Vanden Abeele - Christian Slomianny - Matthieu Flourakis - John Hesketh - Etienne Dewailly - Natal

Source: https://hal.archives-ouvertes.fr/



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