Crosstalk of endoplasmic reticulum exit sites and cellular signaling

Centonze, Federica Grazia; Farhan, Hesso

doi:10.1002/1873-3468.13569

Cited by 18 publications

(14 citation statements)

References 64 publications

(77 reference statements)

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“…With accumulating evidence of the role of cellular trafficking machinery in multiple signaling pathways, it is now well-known that several organelles house and transport cellular signaling molecules [107][108][109][110][111] and thus, they may act as signaling hubs for crosstalk between multiple cell signaling pathways. Here, we present the crosstalk of mTOR and RLR-signaling pathways by demonstrating the requirement of TFG for the interaction of TRAF3 and TBK1 with mTOR upon viral infection.…”

Section: Plos Pathogensmentioning

confidence: 99%

TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response

et al. 2021

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Antiviral innate immune response to RNA virus infection is supported by Pattern-Recognition Receptors (PRR) including RIG-I-Like Receptors (RLR), which lead to type I interferons (IFNs) and IFN-stimulated genes (ISG) production. Upon sensing of viral RNA, the E3 ubiquitin ligase TNF Receptor-Associated Factor-3 (TRAF3) is recruited along with its substrate TANK-Binding Kinase (TBK1), to MAVS-containing subcellular compartments, including mitochondria, peroxisomes, and the mitochondria-associated endoplasmic reticulum membrane (MAM). However, the regulation of such events remains largely unresolved. Here, we identify TRK-Fused Gene (TFG), a protein involved in the transport of newly synthesized proteins to the endomembrane system via the Coat Protein complex II (COPII) transport vesicles, as a new TRAF3-interacting protein allowing the efficient recruitment of TRAF3 to MAVS and TBK1 following Sendai virus (SeV) infection. Using siRNA and shRNA approaches, we show that TFG is required for virus-induced TBK1 activation resulting in C-terminal IRF3 phosphorylation and dimerization. We further show that the ability of the TRAF3-TFG complex to engage mTOR following SeV infection allows TBK1 to phosphorylate mTOR on serine 2159, a post-translational modification shown to promote mTORC1 signaling. We demonstrate that the activation of mTORC1 signaling during SeV infection plays a positive role in the expression of Viperin, IRF7 and IFN-induced proteins with tetratricopeptide repeats (IFITs) proteins, and that depleting TFG resulted in a compromised antiviral state. Our study, therefore, identifies TFG as an essential component of the RLR-dependent type I IFN antiviral response.

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Section: Plos Pathogensmentioning

confidence: 99%

TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response

et al. 2021

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“…As the first station of the secretory pathway, it provides budding platforms for COPII coated vesicles that ensure delivery of proteins and lipids to other organelles in the cell (McCaughey and Stephens, 2019). The ER is also a target of signals emanating from extracellular and intracellular stimuli, and of autoregulatory signals from the organelle itself (Centonze and Farhan, 2019).…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

Endomembranes: Unsung Heroes of Mechanobiology?

Phuyal

Baschieri

2020

Front. Bioeng. Biotechnol.

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Mechanical stimuli have profound effects on the cellular architecture and functions. Over the past two decades, considerable progress has been made in unraveling the molecular machineries that confer cells the ability to sense and transduce mechanical input into biochemical signals. This has resulted in the identification of several forcesensing proteins or mechanically activated ion channels distributed throughout most cell types, whereby the plasma membrane, cytoskeleton, and the nucleus have garnered much attention. Although organelles from the endomembrane system make up significant portion of cell volume and play pivotal roles in the spatiotemporal distribution of signaling molecules, they have received surprisingly little attention in mechanobiology. In this mini-review, we summarize results that document participation of the endomembrane system in sensing and responding to mechanical cues.

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“…The process is completed by recruitment of the Sec13-Sec31 heterotetramer that then helps deform the membrane and facilitates budding of the COPII carrier (8). While ER export was considered long to be a constitutive process, there is mounting evidence that it is subject to regulation by multiple signaling cascades (9)(10)(11)(12)(13). Apart from being the first step of a secretory journey, ER export plays another important homeostatic role, namely by unloading the ER and thereby preventing overload of this compartment.…”

Section: The Er Proteostasis Networkmentioning

confidence: 99%

Tyrosine kinase signaling in and on the endoplasmic reticulum

Farhan

2020

Biochemical Society Transactions

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Tyrosine kinases are signaling molecules that are common to all metazoans and are involved in the regulation of many cellular processes such as proliferation and survival. While most attention has been devoted to tyrosine kinases signaling at the plasma membrane and the cytosol, very little attention has been dedicated to signaling at endomembranes. In this review, I will discuss recent evidence that we obtained on signaling of tyrosine kinases at the surface of the endoplasmic reticulum (ER), as well as in the lumen of this organelle. I will discuss how tyrosine kinase signaling might regulate ER proteostasis and the implication thereof to general cell physiology.

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Crosstalk of endoplasmic reticulum exit sites and cellular signaling

Cited by 18 publications

References 64 publications

TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response

TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response

Endomembranes: Unsung Heroes of Mechanobiology?

Tyrosine kinase signaling in and on the endoplasmic reticulum

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