Regulation of Toll and Toll-like receptor signaling by the endocytic pathway

Lund, Viktor K.; DeLotto, Robert

doi:10.4161/sgtp.2.2.15378

Cited by 14 publications

(8 citation statements)

References 38 publications

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“…Several ESCRT factors are known to be versatile, multifunctional, with pleiotropic effects on multiple targets. For example, the implications of ESCRT complexes in signaling pathways were well-documented [ 51 – 53 ]. In the case of the ESCRT-0 component, it could serve as a positive and negative regulator of RTK signaling during Drosophila development [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

et al. 2015

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The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1–147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1–147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex.

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Section: Discussionmentioning

confidence: 99%

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

et al. 2015

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“…Live imaging studies in Drosophila revealed that Toll not only localizes to the plasma membrane, but also to cytoplasmic vesicles overlapping with Rab5 positive early endosomes. Compared to wild‐type Toll, the localization of the constitutively active variant of Toll10b is shifted towards internal endosomal compartments, suggesting that the subcellular localization of the Toll receptor is a function of its state of activation and that the endocytotic machinery is essential for Toll signalling .…”

Section: Unique Endosomal Characteristicsmentioning

confidence: 99%

Do signalling endosomes play a role in T cell activation?

2013

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Signalling endosomes represent a general mechanism for modulating and compartmentalizing cell signalling, which is achieved by delineating specific spatial environments and connecting the plasma membrane with intracellular events. The molecular composition of vesicles, together with their targeting mechanisms and endocytic routes, contributes to the outcome of signalling pathways that are initiated either at the plasma membrane or within endosomes themselves. In T cell signalling, it is now accepted that the spatial distribution of signalling proteins is central to T cell activation not only at the immunological synapse, but also in endosomes travelling to and from the plasma membrane. In addition, there is a global rearrangement of the endosome machinery upon T cell activation, and emerging experimental evidence suggests that vesicles in T cells contain key T cell signalling proteins. We review the various mechanisms by which endosomes contribute to signalling pathways and consider whether signalling endosomes play a role in T cell signalling.

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“…It also regulates trafficking of many membrane proteins implicated in trans-membrane transport, such as receptors for low-density lipoprotein and transferrin, transporters for amino acids, uric acid, glutamate, glucose, phosphate and cholesterol, and water channels, to control nutrient supply and metabolite discharge (Takata et al, 2008;Gournas et al, 2010;Tachiyama et al, 2011;Koumanov et al, 2012;Sorrentino et al, 2013;Cardona-Lopez et al, 2015;Llinares et al, 2015). It can also regulate trafficking of immune molecules, such as macrophage colony stimulating factor-1, transforming growth factor, Toll/Toll-like and T-cell receptors, and major histocompatibility complex (MHC) class II antigen, to modulate innate and adaptive immunity (Lund and Delotto, 2011;ten Broeke et al, 2013;Lou et al, 2014;Balogh et al, 2015;Wi et al, 2016). Moreover, the MVB pathway can be merged with autophagy for degradation of damaged proteins or subcellular organelles to deal with various stresses (Muller et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Vacuolar protein sorting 4 is required for silkworm metamorphosis

Xia

Chen

Shao

et al. 2019

Insect Molecular Biology

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Vacuolar protein sorting 4 (Vps4) not only functions with its positive regulator vacuolar protein sorting 20‐associated 1 (Vta1) in the multivesicular body (MVB) pathway but also participates alone in MVB‐unrelated cellular processes. However, its physiological roles at the organism level remain rarely explored. We previously identified their respective homologues Bombyx mori Vps4 (BmVps4) and BmVta1 from the silkworm, a model organism for insect research. In this study, we performed fluorescence quantitative real‐time PCR and Western blot to globally characterize the transcription and protein expression profiles of BmVps4 and BmVta1 during silkworm development and in different silkworm tissues and organs. The results showed that they were significantly up‐regulated in metamorphosis, adulthood and embryogenesis relative to larval stages, and displayed a roughly similar tissue‐and‐organ specificity for transcriptions in silkworm larvae. Importantly, BmVps4 was down‐regulated during the early period of the fifth instar, reaching the lowest level of transcription on Day 6, then up‐regulated from Day 7 to the wandering, spinning and pupal stages, and down‐regulated again in adulthood. Moreover, knocking down BmVps4 by RNA interference significantly inhibited silk gland growth, shortened spinning time, prolonged pupation, reduced pupal size and weight, and increased moth wing defects. Together, our data demonstrate the critical and broad requirements for BmVps4 in silkworm metamorphosis.

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Regulation of Toll and Toll-like receptor signaling by the endocytic pathway

Cited by 14 publications

References 38 publications

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

Do signalling endosomes play a role in T cell activation?

Vacuolar protein sorting 4 is required for silkworm metamorphosis

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