R‐SNARE ykt6 resides in membrane‐associated protease‐resistant protein particles and modulates cell cycle progression when over‐expressed

Thayanidhi, Nandhakumar; Liang, Yingjian; Hasegawa, Haruki; Nycz, Deborah C.; Oorschot, Viola; Klumperman, Judith; Hay, Jesse

doi:10.1111/boc.201100048

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…2b ). Among the genes with the highest overexpression in FMDV carriers were serine/arginine-rich splicing factor 9 (SRSF 9), high mobility group nucleosome binding domain 5 (HMGN5), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), zinc finger protein 280B (ZNF280B), hairy/enhancer-of-split related with YRPW motif-like (HEYL), and YKT6 v-SNARE homolog (YKT6), which have all been associated with tumor progression and the inhibition of pathways that promote apoptosis and regulation of cellular growth 66 – 71 . Contrastingly, genes within this functional category that were overexpressed in non-carriers were generally promoters of apoptosis or inhibitors of cell growth (Table 4 Fig.…”

Section: Resultsmentioning

confidence: 99%

Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

Stenfeldt

Eschbaumer

Smoliga

et al. 2017

Sci Rep

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Long-term persistent viral infections cause substantial morbidity and associated economic losses in human and veterinary contexts. Yet, the mechanisms associated with establishment of persistent infections are poorly elucidated. We investigated immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in micro-dissected compartments of the bovine nasopharynx by microarray. The use of laser-capture microdissection allowed elucidation of differential gene regulation within distinct anatomic compartments critical to FMDV infection. Analysis of samples from transitional and persistent phases of infection demonstrated significant differences in transcriptome profiles of animals that cleared infection versus those that became persistently infected carriers. Specifically, it was demonstrated that clearance of FMDV from the nasopharyngeal mucosa was associated with upregulation of targets associated with activation of T cell-mediated immunity. Contrastingly, gene regulation in FMDV carriers suggested inhibition of T cell activation and promotion of Th2 polarization. These findings were corroborated by immunofluorescence microscopy which demonstrated relative abundance of CD8 + T cells in the nasopharyngeal mucosa in association with clearance of FMDV. The findings presented herein emphasize that a critical balance between Th1 and Th2 -mediated immunity is essential for successful clearance of FMDV infection and should be considered for development of next-generation vaccines and antiviral products.Foot-and-mouth disease virus (FMDV), the prototype Aphthovirus within the Picornaviridae family, is the causal agent of foot-and-mouth disease (FMD), a highly contagious disease of cloven-hoofed animals 1 . The endemic presence of FMD in large regions of the world compromises food security and animal welfare. Additionally, as a country's official FMD status defines access to international markets for export of animal products, this disease has a substantial global economic impact on agricultural production and trade.Control and eradication of FMD is impeded by the existence of a prolonged subclinical persistent phase of infection in ruminant species 2-4 . This concept, generally referred to as the FMDV carrier state, is specifically problematic when vaccination is used to control FMD in non-endemic regions as vaccinated cattle may maintain subclinical FMDV persistence following virus exposure, despite having been protected against the clinical disease 5-12 . Confirmed evidence of FMDV transmission from persistently infected cattle is lacking. However, because infectious FMDV is detectable in oropharyngeal fluid (OPF) and nasopharyngeal tissues of carriers for prolonged periods of time, the presence of such animals precludes achieving an official status as FMD-free by the international organization for animal health (OIE) 13 .In cattle, persistent FMDV has been localized to the follicle-associated epithelium (FAE) of the nasopharyngeal mucosa 10,11 or associated lymph nodes ...

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Section: Resultsmentioning

confidence: 99%

Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

Stenfeldt

Eschbaumer

Smoliga

et al. 2017

Sci Rep

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“…In addition, other recent findings demonstrate that, in neurons, a fraction of the soluble pool of Ykt6 is redirected to large membrane-associated particle aggregates that do not colocalize with any of the known components of the endomembrane system (Hasegawa et al, 2003;Thayanidhi et al, 2012). There, Ykt6 does not function as a SNARE protein, but instead, its aggregation has been proposed to act as a buffering mechanism to ensure that high levels of the protein are available to mediate its protective role, at the same time preventing its general overexpression, which is toxic to the cell (Thayanidhi et al, 2012). The unique mode of insertion of Ykt6 into membranes is ideally suited to perform such a protective function.…”

Section: Sec24mentioning

confidence: 97%

“…In contrast to having a protective role in Parkinson's disease, Ykt6 is found to be upregulated in metastatic tumours (Kluger et al, 2004;Ooe et al, 2007), and moreover, overexpression of Ykt6 in epithelial cell lines accelerates the cell cycle (Thayanidhi et al, 2012). In addition, other recent findings demonstrate that, in neurons, a fraction of the soluble pool of Ykt6 is redirected to large membrane-associated particle aggregates that do not colocalize with any of the known components of the endomembrane system (Hasegawa et al, 2003;Thayanidhi et al, 2012). There, Ykt6 does not function as a SNARE protein, but instead, its aggregation has been proposed to act as a buffering mechanism to ensure that high levels of the protein are available to mediate its protective role, at the same time preventing its general overexpression, which is toxic to the cell (Thayanidhi et al, 2012).…”

Section: Sec24mentioning

confidence: 99%

“…In addition, Ykt6 can functionally replace Sec22b in ER-toGolgi trafficking (Liu and Barlowe, 2002) and is a more effective suppressor of α-synuclein toxicity than Sec22b (Thayanidhi et al, 2010). In contrast to having a protective role in Parkinson's disease, Ykt6 is found to be upregulated in metastatic tumours (Kluger et al, 2004;Ooe et al, 2007), and moreover, overexpression of Ykt6 in epithelial cell lines accelerates the cell cycle (Thayanidhi et al, 2012). In addition, other recent findings demonstrate that, in neurons, a fraction of the soluble pool of Ykt6 is redirected to large membrane-associated particle aggregates that do not colocalize with any of the known components of the endomembrane system (Hasegawa et al, 2003;Thayanidhi et al, 2012).…”

Section: Sec24mentioning

confidence: 99%

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Structure and function of longin SNAREs

Daste

Galli

Tareste

2015

Journal of Cell Science

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Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core membrane fusion machinery of intracellular transport and intercellular communication.A little more than ten years ago, it was proposed that the long N-terminal domain of a subset of SNAREs, henceforth called the longin domain, could be a crucial regulator with multiple functions in membrane trafficking. Structural, biochemical and cell biology studies have now produced a large set of data that support this hypothesis and indicate a role for the longin domain in regulating the sorting and activity of SNAREs. Here, we review the first decade of structurefunction data on the three prototypical longin SNAREs: Ykt6, VAMP7 and Sec22b. We will, in particular, highlight the conserved molecular mechanisms that allow longin domains to fold back onto the fusioninducing SNARE coiled-coil domain, thereby inhibiting membrane fusion, and describe the interactions of longin SNAREs with proteins that regulate their intracellular sorting. This dual function of the longin domain in regulating both the membrane localization and membrane fusion activity of SNAREs points to its role as a key regulatory module of intracellular trafficking.

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“…Vac8, a phosphorylated and palmitoylated vacuolar membrane protein, is involved in efficient vacuole fusion, inheritance, and cytosol-to-vacuole trafficking (12,13,20). Ykt6 is a vacuolar SNARE that mediates its own protein palmitoylation during an early stage of homotypic vacuole fusion (21)(22)(23)(24)(25). The t-SNARE Vam3 is palmitoylated and functions with Vam7p in vacuolar protein trafficking and mediates docking/fusion of late transport intermediates with the vacuole (26,27), and Meh1/Ego1 is a palmitoylated vacuolar protein involved in regulating autophagy (28,29).…”

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confidence: 99%

Distinct Palmitoylation Events at the Amino-terminal Conserved Cysteines of Env7 Direct Its Stability, Localization, and Vacuolar Fusion Regulation in S. cerevisiae

Manandhar

Calle

Gharakhanian

2014

Journal of Biological Chemistry

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Background: Env7 is a conserved palmitoylated kinase that regulates vacuolar fusion. Results: Specific Env7 palmitoylated cysteines direct its membrane localization, stability, and function. Conclusion: Distinct palmitoylation events direct Env7 membrane localization as well as its stability and function at the membrane. Significance: This may represent the largest set of functions attributed to palmitoylated cysteines in a single protein.

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R‐SNARE ykt6 resides in membrane‐associated protease‐resistant protein particles and modulates cell cycle progression when over‐expressed

Cited by 10 publications

References 34 publications

Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

Structure and function of longin SNAREs

Distinct Palmitoylation Events at the Amino-terminal Conserved Cysteines of Env7 Direct Its Stability, Localization, and Vacuolar Fusion Regulation in S. cerevisiae

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