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Wenyang Hou, Swati Gupta, Marie-Claude Beauchamp, Libin Yuan, Loydie A Jerome-Majewska
The transmembrane emp24 domain/p24 (TMED) family are essential components of the vesicular transport machinery. Members of the TMED family serve as cargo receptors implicated in selection and packaging of endoplasmic reticulum (ER) luminal proteins into coatomer (COP) II coated vesicles for anterograde transport to the Golgi. Deletion or mutations of Tmed genes in yeast and Drosophila results in ER-stress and activation of the unfolded protein response (UPR). The UPR leads to expression of genes and proteins important for expanding the folding capacity of the ER, degrading misfolded proteins, and reducing the load of new proteins entering the ER...
2017: PloS One
S Saran, D D H Tran, F Ewald, A Koch, A Hoffmann, M Koch, B Nashan, T Tamura
Hepatocellular carcinoma (HCC) is a frequent form of cancer with a poor prognosis and with limited possibilities of medical intervention. It has been shown that over 100 putative driver genes are associated with multiple recurrently altered pathways in HCC, suggesting that multiple pathways will need to be inhibited for any therapeutic method. mRNA processing is regulated by a complex RNA-protein network that is essential for the maintenance of homeostasis. THOC5, a member of mRNA export complex, has a role in less than 1% of mRNA processing, and is required for cell growth and differentiation, but not for cell survival in normal fibroblasts, hepatocytes and macrophages...
July 21, 2016: Oncogene
Gönül Gürol, Duygu Özel Demiralp, Ayça Kasapoğlu Yılmaz, Özlem Akman, Nurbay Ateş, Ayşe Karson
The aim of this study was to investigate cellular proteins in the pathogenesis of the genetic rat model of absence epilepsy. Protein spots were identified with peptide mass fingerprinting analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry. Data were gathered from the frontoparietal cortex and thalamus of Wistar Albino Glaxo/Rij (WAG/Rij) and Wistar by using two-dimensional gel electrophoresis (2D-PAGE). Six proteins (Clathrin light chain-A protein, Transmembrane EMP24 Domain-Containing Protein, Stathmin-4, Myosin Light Chain4, Rheb, phosphoserine phosphatase) were found to be differentially expressed in the frontoparietal cortex of WAG/Rij and Wistar rats in both age groups...
March 2015: Journal of Molecular Neuroscience: MN
João Fadista, Petter Vikman, Emilia Ottosson Laakso, Inês Guerra Mollet, Jonathan Lou Esguerra, Jalal Taneera, Petter Storm, Peter Osmark, Claes Ladenvall, Rashmi B Prasad, Karin B Hansson, Francesca Finotello, Kristina Uvebrant, Jones K Ofori, Barbara Di Camillo, Ulrika Krus, Corrado M Cilio, Ola Hansson, Lena Eliasson, Anders H Rosengren, Erik Renström, Claes B Wollheim, Leif Groop
Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion...
September 23, 2014: Proceedings of the National Academy of Sciences of the United States of America
Ardiyanto Liaunardy-Jopeace, Clare E Bryant, Nicholas J Gay
Toll-like receptor 4 (TLR4), the receptor for the bacterial product endotoxin, is subject to multiple points of regulation at the levels of signaling, biogenesis, and trafficking. Dysregulation of TLR4 signaling can cause serious inflammatory diseases, such as sepsis. We found that the p24 family protein TMED7 (transmembrane emp24 protein transport domain containing 7) is required for the trafficking of TLR4 from the endoplasmic reticulum to the cell surface through the Golgi. TMED7 formed a stable complex with the ectodomain of TLR4, an interaction that required the coiled-coil and Golgi dynamics (GOLD) domains, but not the cytosolic, coat protein complex II (COP II) sorting motif, of TMED7...
July 29, 2014: Science Signaling
Anna Osiecka-Iwan, Justyna Niderla-Bielinska, Anna Hyc, Stanislaw Moskalewski
Rabbit serum produced after transplantation of isolated rat chondrocytes [sensitized rabbit serum (SRS)] demonstrated M r ~ 74- and ~23-kDa (western blot analysis) antigens in rat chondrocyte extracts. Only the latter remained after reduction in 2-mercaptoethanol. Protein sequence analysis of 23-kDa chondrocyte-associated antigen (CAA) revealed that it corresponds to transmembrane Tmp21 protein belonging to the p24 protein family. These proteins mainly participate in the traffic between the endoplasmic reticulum and Golgi complex and in some cells appear also in the membrane of secretory granules and plasmalemma...
March 2014: Calcified Tissue International
Ryogo Hirata, Coh-ichi Nihei, Akihiko Nakano
p24 family proteins are evolutionarily conserved transmembrane proteins involved in the early secretory pathway. Saccharomyces cerevisiae has 8 known p24 proteins that are classified into four subfamilies (p24α, -β, -γ, and -δ). Emp24 and Erv25 are the sole members of p24β and -δ, respectively, and deletion of either destabilizes the remaining p24 proteins, resulting in p24 null phenotype (p24Δ). We studied genetic and physical interactions of p24α (Erp1, -5, and -6) and γ (Erp2, -3, and -4). Deletion of the major p24α (Erp1) partially inhibited p24 activity as reported previously...
December 27, 2013: Journal of Biological Chemistry
Sarah L Doyle, Harald Husebye, Dympna J Connolly, Terje Espevik, Luke A J O'Neill, Anne F McGettrick
Toll-like receptor 4 is an innate immune receptor responsible for the recognition of the Gram-negative cell wall component lipopolysaccharide. Here we show that transmembrane emp24 domain-containing protein 7 (TMED7) inhibits MyD88-independent toll-like receptor 4 signalling. TMED7 overexpression inhibits the ability of TRAM, an adaptor utilized by toll-like receptor 4, or lipopolysaccharide to activate the interferon regulatory factor 3-signalling pathway, whereas TMED7 knockdown enhances production of the cytokine, RANTES, following lipopolysaccharide stimulation...
2012: Nature Communications
A Zakariyah, W Hou, R Slim, L Jerome-Majewska
Members of the transmembrane emp24 domain (Tmed)/p24 family of proteins are required for transport of proteins between the endoplasmic reticulum and the Golgi. One member of this family, Tmed2/p24β1, is expressed during placental development in mice and its expression is required for normal development of the labyrinth layer. Although TMED2 is conserved in humans, little is known about its expression and function in human placenta. We examined TMED2 expression in human placenta between 5.5 and 40 weeks of gestation and showed that TMED2 is expressed in syncytiotrophoblast, cytotrophoblast, and stromal cells...
March 2012: Placenta
Xiaochun Wang, Rongze Yang, Sanjay B Jadhao, Daozhan Yu, Hong Hu, Nicole Glynn-Cunningham, Carole Sztalryd, Kristi D Silver, Da-Wei Gong
OBJECTIVES: The objective of the study was to identify pancreatic islet-selective gene(s) that may play a functional role in islet biology and diabetes development. METHODS: Through bioinformatics, we identified and cloned a pancreas-enriched complementary DNA encoding transmembrane emp24 protein transport domain 6 (TMED6) and examined its mRNA and protein expression in tissues and islet cell lines by Northern analysis and immunofluorescence histochemistry. We also studied the role of TMED6 in insulin secretion using a knockdown approach and its gene expression changes during the development of diabetes in Goto-Kakizaki rats...
January 2012: Pancreas
Fillip Port, George Hausmann, Konrad Basler
Wnt proteins are secreted, lipid-modified glycoproteins that control animal development and adult tissue homeostasis. Secretion of Wnt proteins is at least partly regulated by a dedicated machinery. Here, we report a genome-wide RNA interference screen for genes involved in the secretion of Wingless (Wg), a Drosophila Wnt. We identify three new genes required for Wg secretion. Of these, Emp24 and Eclair are required for proper export of Wg from the endoplasmic reticulum (ER). We propose that Emp24 and Eca act as specific cargo receptors for Wg to concentrate it in forming vesicles at sites of ER export...
November 2011: EMBO Reports
Rong Tan, Dingquan Zou, Yetian Chang
OBJECTIVE: To analyze the morphine rabbit myocardium with matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Six New Zealand white rabbits were randomly assigned to a control group (Group C) and a morphine group (Group M). Group C were pretreated with bolus injection of saline 1 mL/kg. Group M were pretreated with bolus injection of morphine 3 mg/kg. The myocardium tissue proteins of the rabbits 24 hours after the injection of morphine or saline preconditioned were extracted and separated by two dimensional gel electrophoresis(2-DE), and the images were analyzed and different proteins were found...
June 2010: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Elena Kurbatova, Marleen Otzen, Ida J van der Klei
Emp24 is a member of the p24 protein family, which was initially localized to the endoplasmic reticulum, Golgi and COP vesicles, but has recently shown to be associated with Saccharomyces cerevisiae peroxisomes as well. Using cell fractionation and electron- and fluorescence microscopy, we show that in the yeast Hansenula polymorpha, Emp24 also associates with peroxisomes. In addition, we show that peroxisome numbers are strongly decreased in H. polymorpha cells lacking two proteins of the p24 complex, Emp24 and Erp3...
October 6, 2009: FEBS Letters
Anne T Saber, Sabina Halappanavar, Janne K Folkmann, Jette Bornholdt, Anne Mette Z Boisen, Peter Møller, Andrew Williams, Carole Yauk, Ulla Vogel, Steffen Loft, Håkan Wallin
BACKGROUND: Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) - or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver...
2009: Particle and Fibre Toxicology
Marleen Otzen, Arjen M Krikken, Paulina Z Ozimek, Elena Kurbatova, Shirisha Nagotu, Marten Veenhuis, Ida J van der Klei
The peroxin Pex19p is important for the formation of functional peroxisomal membranes. Here we show that Hansenula polymorpha Pex19p is also required for peroxisome inheritance. Peroxisome inheritance is partly defective when Pex19p farnesylation is blocked, whereas deletion of PEX19 resulted in a severe defect in partitioning of peroxisomal structures. Time lapse imaging revealed that in newly formed buds, which had not inherited a peroxisome from the mother cell, new peroxisomes are formed that derive from the nuclear envelope/endoplasmic reticulum...
December 2006: FEMS Yeast Research
Ginger E Carney, Nathan J Bowen
The p24 transmembrane proteins, also known as EMP24/GP25 (endomembrane protein precursor of 24kD (Schimmoller et al., 1995)) proteins, are components of coat protein (COP)-coated vesicles and are present in species as diverse as fungi, plants, flies, worms, and mammals, indicating that they have important conserved functions. Genetic, molecular, and biochemical characterization of these proteins and the loci that encode them has provided insights into their potential cellular roles, including postulated functions in vesicle cargo protein selection and sorting, COPI and COPII vesicle formation and budding, and quality control of proteins that mature through the secretory pathway...
May 2004: Biology of the Cell
Ginger E Carney, Barbara J Taylor
A newly characterized Drosophila melanogaster gene, logjam (loj), functions in female reproduction by modulating oviposition behavior. The locus encodes at least six overlapping transcripts with unique 5' ends. P-element mutants that express very low levels of loj transcripts are unable to oviposit mature eggs. This phenotype can be rescued by the introduction of a transgene expressing the most abundant loj transcript. As for many genes that specify behavioral outputs, loj is present in the adult central nervous system (CNS)...
May 2003: Genetics
Elena Friedmann, Yehuda Salzberg, Adina Weinberger, Shmuel Shaltiel, Jeffrey E Gerst
The OS-9 gene maps to a region (q13-15) of chromosome 12 that is highly amplified in human osteosarcomas and encodes a protein of unknown function. Here we have characterized a homolog designated as YOS9 (YDR057w) from Saccharomyces cerevisiae. The yeast protein (Yos9) is a membrane-associated glycoprotein that localizes to the endoplasmic reticulum (ER). YOS9 interacts genetically with genes involved in ER-Golgi transport, particularly SEC34, whose temperature-sensitive mutant is rescued by YOS9 overexpression...
September 20, 2002: Journal of Biological Chemistry
Vivek Anantharaman, L Aravind
BACKGROUND: Members of the p24 (p24/gp25L/emp24/Erp) family of proteins have been shown to be critical components of the coated vesicles that are involved in the transportation of cargo molecules from the endoplasmic reticulum to the Golgi complex. The p24 proteins form hetero-oligomeric complexes and are believed to function as receptors for specific secretory cargo. RESULTS: Using sensitive sequence-profile analysis methods, we identified a novel beta-strand-rich domain, the GOLD (Golgi dynamics) domain, in the p24 proteins and several other proteins with roles in Golgi dynamics and secretion...
2002: Genome Biology
M Muñiz, C Nuoffer, H P Hauri, H Riezman
Members of the yeast p24 family, including Emp24p and Erv25p, form a heteromeric complex required for the efficient transport of selected proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. The specific functions and sites of action of this complex are unknown. We show that Emp24p is directly required for efficient packaging of a lumenal cargo protein, Gas1p, into ER-derived vesicles. Emp24p and Erv25p can be directly cross-linked to Gas1p in ER-derived vesicles. Gap1p, which was not affected by emp24 mutation, was not cross-linked...
March 6, 2000: Journal of Cell Biology
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