TM9 family proteins control surface targeting of glycine-rich transmembrane domains

Perrin, Jackie; Coadic, Marion Le; Vernay, Alexandre; Dias, Marco Aurélio Dessimoni; Gopaldass, Navin Andréw; Ouertatani-Sakouhi, Hajer; Cosson, Pierre

doi:10.1242/jcs.164848

Cited by 23 publications

(31 citation statements)

References 38 publications

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“…During the infection course, we identified an early response consisting in the upregulation of transcription of a large collection of phagocytosis and lysosome related genes (phg1A, AlyA, B, C, D) (Perrin et al, 2015). In addition, consistent with the report that ESCRT plays an important role in membrane repair during M. marinum infection, many of the ESCRT components were induced .…”

Section: Marinum Infection Induces a Damage And Stress Response Insupporting

confidence: 83%

Time-resolved RNA-seq profiling of the infection of Dictyostelium discoideum by Mycobacterium marinum reveals an integrated host response to damage and stress

Hanna¹,

Burdet²,

Melotti

et al. 2019

Preprint

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Tuberculosis remains the most pervasive infectious disease and the recent emergence of multiple drugresistant strains emphasizes the need for more efficient drug treatments. The experimentally versatile Dictyostelium discoideum -Mycobacterium marinum infection model provides a powerful system to study mycobacteria pathogenicity and host response. In this study, a time-resolved transcriptomic analysis of the amoeba D. discoideum was performed to decipher the different host pathways impacted during infection. We investigated how D. discoideum fine-tunes its gene expression in response to M. marinum infection by assessing the transcriptomic profile covering the critical stages of entry, establishment of a permissive niche, proliferation and dissemination (1, 3, 6, 12, 24 and 48 hours post infection). Differential gene expression provided a fingerprint of the transcriptome of the host cell in the presence of mycobacteria, and helped identify specific markers and molecular signatures of infection. Enrichment pathway analysis showed that most of the Biological Processes (BP) of upregulated genes at early time point of infection hinted towards damage response and cellular defence, especially in specific pathways involved in membrane repair (ESCRT) and bacteria elimination (autophagy). Whereas at late time points of infection, BP related to starvation were upregulated. Some other signatures were more unexpected, such as cell cycle (downregulation of cytosolic large & small ribosomal subunits) and upregulation of metabolic adaptations (lipids transport).

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Section: Marinum Infection Induces a Damage And Stress Response Insupporting

confidence: 83%

Time-resolved RNA-seq profiling of the infection of Dictyostelium discoideum by Mycobacterium marinum reveals an integrated host response to damage and stress

Hanna¹,

Burdet²,

Melotti

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…In this regard, both proximity ligation assay (Figures 5c and d) and subcellular immune-colocalization experiments ( Supplementary Figures S5A and S6) clearly demonstrated that amino acid starvation reduced the physical interaction of TM9SF4 with mTOR. Based on this, we speculated that TM9SF4, which is partially located in lysosome ( Figure 1c) and is known to modulate vesicular trafficking, 15 may promote mTOR dissociation from lysosome, causing its inactivation. However, this is highly speculative.…”

Section: Discussionmentioning

confidence: 95%

“…14 A recent study suggests that TM9SF4 could serve as intramembrane cargo receptors controlling vesicular trafficking, exocytosis and surface localization of glycine-rich membrane proteins. 15 Autophagy is a highly conserved process essential for cell survival under stress conditions including starvation, hypoxia and intracellular stress. 16 In cancer cells, autophagy is also an adaptive survival mechanism to overcome drug/acidic stressinduced cellular stress and cytotoxicity, including alteration of pH homeostasis.…”

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confidence: 99%

TM9SF4 is a novel factor promoting autophagic flux under amino acid starvation

et al. 2017

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Autophagy is a highly complicated process with participation of large numbers of autophagy-related proteins. Under nutrient starvation, autophagy promotes cell survival by breaking down nonessential cellular components for recycling use. However, due to its high complexity, molecular mechanism of autophagy is still not fully understood. In the present study, we report a novel autophagy-related protein TM9SF4, which plays a functional role in the induction phase of autophagic process. TM9SF4 proteins were abundantly expressed in the kidney, especially in renal proximal tubular epithelial cells. At subcellular cells, TM9SF4 proteins were mostly localized in lysosome, Golgi, late endosome and autophagosome. Knockdown of TM9SF4 with TM9SF4-shRNAs markedly reduced the starvation-induced autophagy in HEK293 cells, the effect of which persisted in the presence of bafilomycin A1. TM9SF4-shRNAs also substantially attenuated the starvation-induced mTOR inactivation. In animal model, starvation was able to induce LC3-II accumulation and cause mTOR inactivation in renal cortical tissue in wild-type mice, the effect of which was minimal/absent in TM9SF4 knockout (TM9SF4) mice. Co-immunoprecipitation and proximity ligation assay demonstrated physical interaction of TM9SF4 proteins with mTOR. In addition, knockdown or knockout of TM9SF4 reduced the starvation-induced cell death in HEK293 cells and animal model. Taken together, the present study identifies TM9SF4 as a novel autophagy-related protein. Under nutrient starvation, TM9SF4 functions to facilitate mTOR inactivation, resulting in an enhanced autophagic flux, which serves to protect cells from apoptotic cell death.

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“…Generation of mNEET KO Cell Lines. We generated mNEET-knockout cell lines using the CRISPR/Cas9 method, as described previously (25). Briefly, a plasmid purchased from DNA2.0 was used, the guide RNA targeting the first exon of mNEET (AGCTCCAACTCCGCTGT*GCGAG; the * represents the cutting site of the Cas9 nuclease).…”

Section: Methodsmentioning

confidence: 99%

MitoNEET-dependent formation of intermitochondrial junctions

Vernay

Marchetti

Sabra

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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MitoNEET (mNEET) is a dimeric mitochondrial outer membrane protein implicated in many facets of human pathophysiology, notably diabetes and cancer, but its molecular function remains poorly characterized. In this study, we generated and analyzed mNEET KO cells and found that in these cells the mitochondrial network was disturbed. Analysis of 3D-EM reconstructions and of thin sections revealed that genetic inactivation of mNEET did not affect the size of mitochondria but that the frequency of intermitochondrial junctions was reduced. Loss of mNEET decreased cellular respiration, because of a reduction in the total cellular mitochondrial volume, suggesting that intermitochondrial contacts stabilize individual mitochondria. Reexpression of mNEET in mNEET KO cells restored the WT morphology of the mitochondrial network, and reexpression of a mutant mNEET resistant to oxidative stress increased in addition the resistance of the mitochondrial network to H 2 O 2 -induced fragmentation. Finally, overexpression of mNEET increased strongly intermitochondrial contacts and resulted in the clustering of mitochondria. Our results suggest that mNEET plays a specific role in the formation of intermitochondrial junctions and thus participates in the adaptation of cells to physiological changes and to the control of mitochondrial homeostasis.mitoNEET | CISD1 | mitochondria | intermitochondrial junctions | endoplasmic reticulum

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TM9 family proteins control surface targeting of glycine-rich transmembrane domains

Cited by 23 publications

References 38 publications

Time-resolved RNA-seq profiling of the infection of Dictyostelium discoideum by Mycobacterium marinum reveals an integrated host response to damage and stress

Time-resolved RNA-seq profiling of the infection of Dictyostelium discoideum by Mycobacterium marinum reveals an integrated host response to damage and stress

TM9SF4 is a novel factor promoting autophagic flux under amino acid starvation

MitoNEET-dependent formation of intermitochondrial junctions

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