Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 27 September 2011
Vol. 4, Issue 192, p. ec271
[DOI: 10.1126/scisignal.4192ec271]

EDITORS' CHOICE

Cell Biology ERK to Conserve Resources

Annalisa M. VanHook

Science Signaling, AAAS, Washington, DC 20005, USA

Starving cells decrease protein synthesis and secretion. Suppression of protein synthesis is mediated by inhibition of the target of rapamycin complex 1 (TORC1), but the regulation of protein secretion by nutrient status is less well understood. Zacharogianni et al. report that extracellular signal–regulated kinase 7 (ERK7) suppresses protein secretion in response to amino acid starvation in both insect (S2) and mammalian (HeLa) cells. The authors identified ERK7 in a screen for kinases required for proper functioning of the early secretory pathway through which proteins are transported from the endoplasmic reticulum (ER) to the Golgi. Overexpression of ERK7 in S2 cells caused dispersion of Sec16 [a protein that is required for secretion and normally localizes to sites where proteins exit the ER en route to the Golgi (tER sites)] and disassembly of tER sites, as did serum or amino acid withdrawal. Depleting ERK7 by RNA interference (RNAi) or expressing a kinase-dead version of ERK7 partially prevented these starvation-induced phenotypes, whereas overexpression of ERK7 enhanced Sec16 dispersion after serum withdrawal in S2 cells. Amino acid and serum starvation also reduced the number of tER sites in HeLa cells, and depleting ERK7 by RNAi reversed this phenotype. In S2 cells overexpressing ERK7, amino acid starvation, like inhibition of the proteasome, increased the abundance of ERK7, suggesting that amino acid starvation may lead to Sec16 dispersion and tER disassembly by stabilizing ERK7. Treating S2 cells with the TORC1 inhibitor rapamycin or depleting the TORC1 component Raptor by RNAi did not affect Sec16 distribution or tER site organization. In human cells, ERK2-mediated phosphorylation of the N terminus of Sec16 enhances secretion, but neither inhibiting signaling through ERK2 nor deleting the ERK2 phosphorylation site in Sec16 affected Sec16 distribution in S2 cells. The authors identified a C-terminal region of Sec16 required for its starvation-induced dispersion in S2 cells, suggesting that this region might be modified by ERK7. These results offer a glimpse into how an environmental stimulus such as nutrient availability may regulate protein secretion, but how nutrient status is sensed and relayed to ERK7 remains to be determined.

M. Zacharogianni, V. Kondylis, Y. Tang, H. Farhan, D. Xanthakis, F. Fuchs, M. Boutros, C. Rabouille, ERK7 is a negative regulator of protein secretion in response to amino-acid starvation by modulating Sec16 membrane association. EMBO J. 30, 3684–3700 (2011). [PubMed]

Citation: A. M. VanHook, ERK to Conserve Resources. Sci. Signal. 4, ec271 (2011).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882