ERK7 is a negative regulator of protein secretion in response to amino-acid starvation by modulating Sec16 membrane association

M. Zacharogianni, V. Kondylis, Y. Tang, H. Farhan, D. Xanthakis, F. Fuchs, M. Boutros, C. Rabouille

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

RNAi screening for kinases regulating the functional organization of the early secretory pathway in Drosophila S2 cells has identified the atypical Mitotic-Associated Protein Kinase (MAPK) Extracellularly regulated kinase 7 (ERK7) as a new modulator. We found that ERK7 negatively regulates secretion in response to serum and amino-acid starvation, in both Drosophila and human cells. Under these conditions, ERK7 turnover through the proteasome is inhibited, and the resulting higher levels of this kinase lead to a modification in a site within the C-terminus of Sec16, a key ER exit site component. This post-translational modification elicits the cytoplasmic dispersion of Sec16 and the consequent disassembly of the ER exit sites, which in turn results in protein secretion inhibition. We found that ER exit site disassembly upon starvation is TOR complex 1 (TORC1) independent, showing that under nutrient stress conditions, cell growth is not only inhibited at the transcriptional and translational levels, but also independently at the level of secretion by inhibiting the membrane flow through the early secretory pathway. These results reveal the existence of new signalling circuits participating in the complex regulation of cell growth. [KEYWORDS: Animals, Cell Line, Drosophila, Drosophila Proteins/ metabolism, Extracellular Signal-Regulated MAP Kinases/ metabolism, Gene Expression Regulation, Microscopy, Fluorescence, Microscopy, Immunoelectron, Proteins/ secretion, Vesicular Transport Proteins/ metabolism]
Originele taal-2Engels
Pagina's (van-tot)3684-3700
TijdschriftEMBO Journal
Volume30
Nummer van het tijdschrift18
DOI's
StatusGepubliceerd - 2011

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