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Ribosome-translocon complex mediates calcium leakage from endoplasmic reticulum stores

Lookup NU author(s): Professor John Hesketh

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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 mag-fura-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.


Publication metadata

Author(s): Van Coppenolle F, Vanden Abeele F, Slomianny C, Flourakis M, Hesketh J, Dewailly E, Prevarskaya N

Publication type: Article

Publication status: Published

Journal: Journal of Cell Science

Year: 2004

Volume: 117

Issue: 18

Pages: 4135-4142

ISSN (print): 0021-9533

ISSN (electronic): 1477-9137

Publisher: The Company of Biologists Ltd

URL: http://dx.doi.org/10.1242/jcs.01274

DOI: 10.1242/jcs.01274

PubMed id: 15280427


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