Emp24

The transmembrane emp24 domain-containing (TMED) proteins, also called p24 proteins, are members of a family of sorting receptors present in all representatives of the Eukarya and abundantly present in all subcompartments of the early secretory pathway, namely the endoplasmic reticulum (ER), the Golgi, and the intermediate compartment. Although essential during the bidirectional transport between the ER and the Golgi, there is still a lack of information regarding the TMED's structure across different subfamilies...

Lung squamous cell carcinoma (LUSC) has a poor clinical prognosis and lacks effective targeted therapy. The transmembrane emp24 trafficking protein 3 (TMED3) belongs to the TMED family, which is responsible for the transport of intracellular proteins. This study was to explore the clinicopathological significance and biological effects of TMED3 in LUSC. Expression of TMED3 in LUSC was detected by immunohistochemical (IHC). The loss-of-function assays were used to investigate the effects of TMED3 on proliferation, apoptosis, cell cycle, and migration of LUSC cells...

Chordoma is a rare low‑grade tumor of the axial skeleton. Over previous decades, a range of targeted drugs have been used for treating chordoma, with more specific and effective therapies under investigation. Transmembrane Emp24 protein transport domain containing 3 (TMED3) is a novel gene reported to be a regulator of oncogenesis, cancer development and metastasis; however, its role in chordoma remains unclear. In the present study, the expression of TMED3 was investigated in chordoma cells, and the effect of TMED3 knockdown on chordoma development was examined in vitro and in vivo , followed by exploration of differentially expressed proteins in TMED3‑silenced chordoma cells via an apoptosis antibody array...

OBJECTIVE: TMED2 is a member of the transmembrane emp24 domain (Tmed)/p24 protein family, which is significantly upregulated in breast cancer, ovarian cancer and other tumour tissues. The purpose of this study was to investigate the expression of TMED2 in MM cell lines and its effect on the biological behaviour of MM cell lines. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of TMED2 in MM cell lines, including MM.1S and RPMI 8226 cells, and lentivirus vector-mediated TMED2 gene silencing was used to further study the effect of the downregulation of TMED2 expression on cell viability, the cell cycle, and apoptosis...

Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues...

Regulated transport through the secretory pathway is essential for embryonic development and homeostasis. Disruptions in this process impact cell fate, differentiation and survival, often resulting in abnormalities in morphogenesis and in disease. Several congenital malformations are caused by mutations in genes coding for proteins that regulate cargo protein transport in the secretory pathway. The severity of mutant phenotypes and the unclear aetiology of transport protein-associated pathologies have motivated research on the regulation and mechanisms through which these proteins contribute to morphogenesis...

The male gamete is not completely mature after ejaculation and requires further events in the female genital tract to acquire fertilizing ability, including the processes of capacitation and acrosome reaction. In order to shed light on protein changes experienced by the sperm cell in preparation for fertilization, a comprehensive quantitative proteomic profiling based on isotopic peptide labeling and liquid chromatography followed by tandem mass spectrometry was performed on spermatozoa from three donors of proven fertility under three sequential conditions: purification with density gradient centrifugation, incubation with capacitation medium, and induction of acrosome reaction by exposure to the calcium ionophore A23187...

Background: We obtained 2 types of clones which were termed SC (sphere-shaped clone) and NSC (non-sphere-shaped clone) from 4T1 cells by monoclonal culture. SC and NSC were distinct in morphology, surface marker, metabolism and proliferation rate. With the transcriptome sequencing data analysis, we found TMED2 expressed higher in SCs. TMED2 was a member of the transmembrane emp24 domain and might play roles in cancer cell proliferation. However, its prognostic roles in breast cancer remained unknown. We aimed to investigate the prognostic values of TMED2 in patients with breast cancer...

Mediator of IRF3 activation (MITA), also known as stimulator of interferon genes (STING), plays a vital role in the innate immune responses to cytosolic dsDNA. The trafficking of MITA from the ER to perinuclear vesicles is necessary for its activation of the downstream molecules, which lead to the production of interferons and pro-inflammatory cytokines. However, the exact mechanism of MITA activation remains elusive. Here, we report that transmembrane emp24 protein transport domain containing 2 (TMED2) potentiates DNA virus-induced MITA signaling...

Peanut wild relatives (Arachis spp.) have high genetic diversity and are important sources of resistance to biotic and abiotic stresses. In this study, proteins were analyzed in root tissues of A. duranensis submitted to a progressive water deficit in soil and the differential abundance was compared to transcript expression profiles obtained by RNA-seq and qRT-PCR. Using a 2-DE approach, a total of 31 proteins were identified, most of which were associated with stress response and drought perception. These comprised a chitinase-2 (unique to stressed condition), an MLP-like protein, a glycine-rich protein DOT1-like, a maturase K and heat shock-related proteins (HSP70 - an isoform unique to the control, and HSP17...

TMED2, a member of the transmembrane emp24 domain (TMED) family, is required for transport of cargo proteins between the ER and Golgi. TMED2 is also important for normal morphogenesis of mouse embryos and their associated placenta, and in fact Tmed2 homozygous mutant embryos arrest at mid-gestation due to a failure of placental labyrinth layer formation. Differentiation of the placental labyrinth layer depends on chorioallantoic attachment (contact between the chorion and allantois), and branching morphogenesis (mingling of cells from these two tissues)...

BACKGROUND: The sensory epithelium of the inner ear converts the mechanical energy of sound to electro-chemical energy recognized by the central nervous system. This process is mediated by receptor cells known as hair cells that express proteins in a timely fashion with the onset of hearing. METHODS: The proteomes of 3, 14, and 30 day-old mice cochlear sensory epithelia were revealed, using label-free quantitative mass spectrometry (LTQ-Orbitrap). Statistical analysis using a one-way ANOVA followed by Bonferroni's post-hoc test was used to show significant differences in protein expression...

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...

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...

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...

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...

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...

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...

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...

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...