title: ERK7 is a negative regulator of protein secretion in response to amino-acid starvation by modulating Sec16 membrane association.
abstract: 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.
authors.affiliation: Department of Cell Biology, Cell microscopy Centre, UMC Utrecht, Heidelberglaan, The Netherlands.
authors.forename: Margarita
authors.initials: M
authors.lastname: Zacharogianni
authors.forename: Vangelis
authors.initials: V
authors.lastname: Kondylis
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.forename: Hesso
authors.initials: H
authors.lastname: Farhan
authors.forename: Despina
authors.initials: D
authors.lastname: Xanthakis
authors.forename: Florian
authors.initials: F
authors.lastname: Fuchs
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.forename: Catherine
authors.initials: C
authors.lastname: Rabouille
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D011506:Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D011506:Proteins; C533274:Sec16 protein, Drosophila; D033921:Vesicular Transport Proteins; D048049:Extracellular Signal-Regulated MAP Kinases