Mon1a Protein Acts in Trafficking through the Secretory Apparatus

Bagley, Dustin; Paradkar, Prasad N.; Kaplan, Jerry

doi:10.1074/jbc.m112.354043

Cited by 10 publications

(15 citation statements)

References 35 publications

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“…A gene-based analysis identified 95 genes from across 28 regions that were significantly associated with Educational Attainment ( Supplementary Table S3 ). The top hit from the gene-based analysis was MON1 secretory trafficking family member A ( MON1A ), involved in membrane trafficking, 60 which is on chromosome 3. The CADM2 gene was also significant.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

et al. 2016

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People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.

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Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

et al. 2016

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“…Nevertheless, acceleration of VSVG intracellular traffic has not been frequently observed in HeLa cells. Depletion of several proteins has yielded to a sequestration into the Golgi apparatus or a delay in VSVG appearance at the plasma membrane . Here, surprisingly, the acceleration of the anterograde traffic in HeLa cells suggests the attractive hypothesis that Yif1B could control a sorting or recycling step, that takes time, occurring just before or after the budding at the Golgi apparatus, or through this compartment, before vesicles are addressed to the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Yif1B Is Involved in the Anterograde Traffic Pathway and the Golgi Architecture

Alterio

Masson

Díaz

et al. 2015

Traffic

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Yif1B is an intracellular membrane-bound protein belonging to the Yip family, shown previously to control serotonin 5-HT 1A receptor targeting to dendrites. Because some Yip proteins are involved in the intracellular traffic between the ER and the Golgi, here we investigated the precise localization of Yif1B in HeLa cells. We found that Yif1B is not resident into the Golgi, but rather belongs to the IC compartment. After analyzing the role of Yif1B in protein transport, we showed that the traffic of the VSVG protein marker was accelerated in Yif1B depleted HeLa cells, as well as in hippocampal neurons from Yif1B KO mice. Conversely, Yif1B depletion in HeLa cells did not change the retrograde traffic of ShTx. Interestingly, in long term depletion of Yif1B as in Yif1B KO mice, we observed a disorganized Golgi architecture in CA1 pyramidal hippocampal neurons, which was confirmed by electron microscopy. However, because short term depletion of Yif1B did not change Golgi structure, it is likely that the implication of Yif1B in anterograde traffic does not rely on its role in structural organization of the Golgi apparatus, but rather on its shuttling between the ER, the IC and the Golgi compartments.

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“…The same expression pattern was found for the gene Rab G3F that together with monensin sensitivity 1( Mon 1) is involved in prevacuolar compartments-to-vacuole trafficking and vacuole biogenesis [ 97 ]. MON1 is also involved in iron homeostasis of animal cells [ 98 , 99 ].…”

Section: Resultsmentioning

confidence: 99%

Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level

2015

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In addition to the micronutrient inadequacy of staple crops for optimal human nutrition, a global downtrend in crop-quality has emerged from intensive breeding for yield. This trend will be aggravated by elevated levels of the greenhouse gas carbon dioxide. Therefore, crop biofortification is inevitable to ensure a sustainable supply of minerals to the large part of human population who is dietary dependent on staple crops. This requires a thorough understanding of plant-mineral interactions due to the complexity of mineral homeostasis. Employing RNA sequencing, we here communicate transfer cell specific effects of excess iron and zinc during grain filling in our model crop plant barley. Responding to alterations in mineral contents, we found a long range of different genes and transcripts. Among them, it is worth to highlight the auxin and ethylene signaling factors Arfs, Abcbs, Cand1, Hps4, Hac1, Ecr1, and Ctr1, diurnal fluctuation components Sdg2, Imb1, Lip1, and PhyC, retroelements, sulfur homeostasis components Amp1, Hmt3, Eil3, and Vip1, mineral trafficking components Med16, Cnnm4, Aha2, Clpc1, and Pcbps, and vacuole organization factors Ymr155W, RabG3F, Vps4, and Cbl3. Our analysis introduces new interactors and signifies a broad spectrum of regulatory levels from chromatin remodeling to intracellular protein sorting mechanisms active in the plant mineral homeostasis. The results highlight the importance of storage proteins in metal ion toxicity-resistance and chelation. Interestingly, the protein sorting and recycling factors Exoc7, Cdc1, Sec23A, and Rab11A contributed to the response as well as the polar distributors of metal-transporters ensuring the directional flow of minerals. Alternative isoform switching was found important for plant adaptation and occurred among transcripts coding for identical proteins as well as transcripts coding for protein isoforms. We also identified differences in the alternative-isoform preference between the treatments, indicating metal-affinity shifts among isoforms of metal transporters. Most important, we found the zinc treatment to impair both photosynthesis and respiration. A wide range of transcriptional changes including stress-related genes and negative feedback loops emphasize the importance to withhold mineral contents below certain cellular levels which otherwise might lead to agronomical impeding side-effects. By illustrating new mechanisms, genes, and transcripts, this report provides a solid platform towards understanding the complex network of plant mineral homeostasis.

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Mon1a Protein Acts in Trafficking through the Secretory Apparatus

Cited by 10 publications

References 35 publications

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Yif1B Is Involved in the Anterograde Traffic Pathway and the Golgi Architecture

Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level

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