A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

Zacharogianni, Margarita; Gomez, A. Aguilera; Veenendaal, Tineke; Smout, Jan; Rabouille, Cathérine

doi:10.7554/elife.04132

Cited by 92 publications

(175 citation statements)

References 62 publications

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“…a strict COPII-dependent emergence of a secretory flux. Although this study focused the role of mitogens in regulating ERES, others have recently identified in Drosophila a novel response of ERES to amino acid starvation (Zacharogianni et al, 2014), which is distinct from the response to serum starvation reported previously (Zacharogianni et al, 2011). Amino acid starvation results in the formation of 'Sec bodies', where Sec16 and other COPII components are stored.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Sec16 levels and dynamics links proliferation and secretion

Tillmann

Reiterer

Baschieri

et al. 2014

Journal of Cell Science

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We currently lack a broader mechanistic understanding of the integration of the early secretory pathway with other homeostatic processes such as cell growth. Here, we explore the possibility that Sec16A, a major constituent of endoplasmic reticulum exit sites (ERES), acts as an integrator of growth factor signaling. Surprisingly, we find that Sec16A is a short-lived protein that is regulated by growth factors in a manner dependent on Egr family transcription factors. We hypothesize that Sec16A acts as a central node in a coherent feed-forward loop that detects persistent growth factor stimuli to increase ERES number. Consistent with this notion, Sec16A is also regulated by short-term growth factor treatment that leads to increased turnover of Sec16A at ERES. Finally, we demonstrate that Sec16A depletion reduces proliferation, whereas its overexpression increases proliferation. Together with our finding that growth factors regulate Sec16A levels and its dynamics on ERES, we propose that this protein acts as an integrator linking growth factor signaling and secretion. This provides a mechanistic basis for the previously proposed link between secretion and proliferation.

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Section: Discussionmentioning

confidence: 99%

Regulation of Sec16 levels and dynamics links proliferation and secretion

Tillmann

Reiterer

Baschieri

et al. 2014

Journal of Cell Science

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“…These dynamic properties of organelles are essential for normal cellular functions, being critical in development (Hanna et al, 2013), differentiation (Forni et al, 2016), mitosis (Jongsma et al, 2015), and various forms of stress response (Farber-Katz et al, 2014; Zacharogianni et al, 2014). Consequently, organelle dysfunction is known to be the driver of severe human diseases, including disorders of the mitochondria (Reeve et al, 2013), endoplasmic reticulum (ER) (Kerbiriou et al, 2007), endosomes (Cataldo et al, 2008), lysosomes (Platt et al, 2012), and peroxisomes (Smith and Aitchison, 2013).…”

Section: Introductionmentioning

confidence: 99%

A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection

2016

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SUMMARY The organelles within a eukaryotic host are manipulated by viruses to support successful virus replication and spread of infection, yet the global impact of viral infection on host organelles is poorly understood. Integrating microscopy, sub-cellular fractionation, mass spectrometry, and functional analyses, we conducted a cell-wide study of organelles in primary fibroblasts throughout the timecourse of human cytomegalovirus (HCMV) infection. We used label-free and isobaric-labeling proteomics to characterize nearly 4,000 host and 100 viral proteins, then classified their specific subcellular locations over time using machine learning. We observed a global reorganization of proteins across the secretory pathway, plasma membrane, and mitochondria, including reorganization and processing of lysosomal proteins into distinct subpopulations and translocations of individual proteins between organelles at specific timepoints. We also demonstrate that MYO18A, an unconventional myosin that translocates from the plasma membrane to the viral assembly complex, is necessary for efficient HCMV replication. This study provides a comprehensive resource for understanding host and virus biology during HCMV pathogenesis.

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“…We then used them to follow PARylation and MARylation in vivo during cellular stresses, with particular focus on amino-acid starvation that induces the formation of a recently described stress assembly, the Sec body (Zacharogianni et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

“…Sec body formation results from the inhibition of a major anabolic pathway, the protein transport through the secretory pathway, upon amino-acid starvation of Drosophila cells (Amodio et al, 2009; Zacharogianni et al, 2014). The secretory pathway ensures the delivery of signal peptide containing proteins to the extracellular medium and the plasma membrane and to nearly all membrane-bound compartments.…”

Section: Introductionmentioning

confidence: 99%

“…The inhibition of protein transport through the secretory pathway upon amino-acid starvation is accompanied by the remodeling of ERES and the formation of a novel type of pro-survival stress assembly with liquid droplet properties, the Sec body, where COPII coat proteins and Sec16 are stored and protected from degradation during the period of stress (Zacharogianni et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

Aguilera-Gomez

Oorschot

Veenendaal

et al. 2016

eLife

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PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress.DOI: http://dx.doi.org/10.7554/eLife.21475.001

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A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation

Cited by 92 publications

References 62 publications

Regulation of Sec16 levels and dynamics links proliferation and secretion

Regulation of Sec16 levels and dynamics links proliferation and secretion

A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection

In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

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