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functional proteins, including cytokines, glycosylated proteins, and extracellular domains of membrane proteins. … knowledge of the field of protein biochemistry (protein characterization, aggregation, glycosylation,… Read more here: functional proteins, including cytokines, glycosylated proteins, and extracellular domains of membrane proteins. … knowledge of the field of protein biochemistry (protein characterization, aggregation, glycosylation,… Read more here:
Am J Physiol Renal Physiol. 2012 Feb 15; The major function of epithelial tissues is to maintain proper ion, solute and water homeostasis. The tubule of the renal nephron has an amazingly simple structure, lined by epithelial cells, yet the segments (i.e., proximal tubule versus collecting duct) of the nephron have unique transport functions. The functional differences are because epithelial cells are polarized, and thus, possess different patterns (distributions) of membrane transport proteins in the apical and basolateral membranes of the cell. K(+) channels play critical roles in normal physiology. Over 90 different genes for K(+) channels have been identified in the human genome. Epithelial K(+) channels can be located within either or both the apical and basolateral membranes of the cell. One of the primary functions of basolateral K(+) channels is to recycle K+ across the basolateral membrane for proper function of the Na(+)/K(+)-ATPase among other functions. Mutations of these channels can cause significant disease. The focus of this review is to provide an overview of the basolateral K(+) channels of the nephron, provide potential physiological functions and pathophysiology of these channels, where appropriate. We have taken a K(+) channel gene family' approach in presenting the representative basolateral K(+) channels of the nephron. The basolateral K(+) channels of the renal epithelia are represented by members of the KCNK, KCNJ, KCNQ, KCNE, and SLO gene families. Read the original post:
Curr Protein Pept Sci. 2012 Feb 2; Proto-oncoproteins are a heterogeneous group of proteins that induce cellular differentiation, proliferation and growth, acting at different points of signaling cascades and in different cell compartments, through many different mechanisms. If the proto-oncogenes that give raise to proto-oncoproteins undergo genetic damage, they become oncogenes and their products are the oncoproteins responsible for cellular transformation in cancer. Some proto-oncoproteins are related to membranes and they exert their function at this level. Among these are receptors and receptor-like growth factors, membrane associated tyrosine kinases, and small GTPases. Other proto-oncoproteins are transcription factors and as such, their best known functional context is promoter DNA regions. Consequently, DNA is widely viewed as their most relevant non protein partner. Any interaction of these proteins with membranes is generally overlooked and, when considered, the membrane is regarded as a reservoir for timely release requiring proteolytic activity. However, this status quo should be revised. Some Immediate-Early proteins that are mobilized in the cell shortly after stimulus are also a subset of the transcription factor kind of proto-oncoproteins. These particular Immediate-Early proto-Oncoproteins (IEOs) exceed strict DNA related functions. Gathering evidence coming from biophysical studies on one hand and from molecular and cellular studies on the other hand, converge suggesting a link between them and membranes. In this review we discuss the conception that transcription factors with the features of IEOs exert their function in cellular processes, not only through association to DNA related to targeted transcription, but also through association to membranes related to global replication and transcription. View original post here:
Curr Protein Pept Sci. 2012 Feb 2; Proto-oncoproteins are a heterogeneous group of proteins that induce cellular differentiation, proliferation and growth, acting at different points of signaling cascades and in different cell compartments, through many different mechanisms. If the proto-oncogenes that give raise to proto-oncoproteins undergo genetic damage, they become oncogenes and their products are the oncoproteins responsible for cellular transformation in cancer. Some proto-oncoproteins are related to membranes and they exert their function at this level. Among these are receptors and receptor-like growth factors, membrane associated tyrosine kinases, and small GTPases. Other proto-oncoproteins are transcription factors and as such, their best known functional context is promoter DNA regions. Consequently, DNA is widely viewed as their most relevant non protein partner. Any interaction of these proteins with membranes is generally overlooked and, when considered, the membrane is regarded as a reservoir for timely release requiring proteolytic activity. However, this status quo should be revised. Some Immediate-Early proteins that are mobilized in the cell shortly after stimulus are also a subset of the transcription factor kind of proto-oncoproteins. These particular Immediate-Early proto-Oncoproteins (IEOs) exceed strict DNA related functions. Gathering evidence coming from biophysical studies on one hand and from molecular and cellular studies on the other hand, converge suggesting a link between them and membranes. In this review we discuss the conception that transcription factors with the features of IEOs exert their function in cellular processes, not only through association to DNA related to targeted transcription, but also through association to membranes related to global replication and transcription. Read the original:
Plant Signal Behav. 2012 Jan 1; 7(1): 31-3 The voltage-dependent anion channels (VDACs) known as a major group of outer mitochondrial membrane proteins are present in all eukaryotic species. In mammalian cells, they have been established as a key player in mitochondrial metabolism and apoptosis regulation. By contrast, little is known about the function of plant VDACs. Recently, we performed functional analysis of all VDAC gene members in Arabidopsis thaliana, and revealed that each AtVDAC member has a specialized function. Especially, in spite of similar subcellular localization and expression profiling of AtVDAC2 and AtVDAC4, both the T-DNA insertion knockout mutants of them, vdac2-2 and vdac4-2, showed severe growth retardation. These results suggest that AtVDAC2 and AtVDAC4 proteins clearly have distinct functions. Here, we introduced the AtVDAC2 gene into the vdac2-2 mutant, and demonstrated that the miniature phenotype of vdac2-2 plant is abolished by AtVDAC2 expression. Excerpt from:
Heart Rhythm. 2012 Jan 30; BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. BIN1 is a membrane associated protein important to cardiomyocyte homeostasis and is down regulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing due to ARVC. OBJECTIVE: To determine whether plasma BIN1 can measure disease severity in patients with ARVC. METHODS: We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to predict cardiac functional status and ventricular arrhythmias. RESULTS: Mean plasma BIN1 levels were decreased in ARVC patients with heart failure (15 ± 7 vs. 60 ± 17 in patients without heart failure, p<0.05; plasma BIN1 is 60±10 in non-ARVC normal controls). BIN1 levels correlated inversely with ventricular arrhythmia (R=-0.47, p<0.05), and low BIN1 correctly classified patients with advanced heart failure or ventricular arrhythmia (ROC Area under the curve, AUC, of 0.88±0.07). Low BIN1 also predicted future ventricular arrhythmias (ROC AUC of 0.89±0.09). In a stratified analysis, BIN1 could predict future arrhythmias in patients without severe heart failure (n=20) with an accuracy of 82 %. In the seven ARVC patients with serial blood samples, all of whom had evidence of disease progression during follow up, plasma BIN1 decreased significantly (decrease of 63 %, p<0.05). CONCLUSIONS: Plasma BIN1 seems to correlate with cardiac functional status and presence or absence of sustained ventricular arrhythmias in a small cohort of ARVC patients and can predict future ventricular arrhythmias. See the original post:
Heart Rhythm. 2012 Jan 30; BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. BIN1 is a membrane associated protein important to cardiomyocyte homeostasis and is down regulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing due to ARVC. OBJECTIVE: To determine whether plasma BIN1 can measure disease severity in patients with ARVC. METHODS: We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to predict cardiac functional status and ventricular arrhythmias. RESULTS: Mean plasma BIN1 levels were decreased in ARVC patients with heart failure (15 ± 7 vs. 60 ± 17 in patients without heart failure, p<0.05; plasma BIN1 is 60±10 in non-ARVC normal controls). BIN1 levels correlated inversely with ventricular arrhythmia (R=-0.47, p<0.05), and low BIN1 correctly classified patients with advanced heart failure or ventricular arrhythmia (ROC Area under the curve, AUC, of 0.88±0.07). Low BIN1 also predicted future ventricular arrhythmias (ROC AUC of 0.89±0.09). In a stratified analysis, BIN1 could predict future arrhythmias in patients without severe heart failure (n=20) with an accuracy of 82 %. In the seven ARVC patients with serial blood samples, all of whom had evidence of disease progression during follow up, plasma BIN1 decreased significantly (decrease of 63 %, p<0.05). CONCLUSIONS: Plasma BIN1 seems to correlate with cardiac functional status and presence or absence of sustained ventricular arrhythmias in a small cohort of ARVC patients and can predict future ventricular arrhythmias. See the original post here: In blood, these RCS can attack many biological macromolecules, such as attacking erythrocyte membrane protein and causing the structural and functional changes. Therefore, it has been proposed that the accumulation of unpairable … However, the detailed biochemical mechanism remains unclear. In order to reveal the mechanism, we determined the alteration of RCS, thiols, carbonylation levels and fluorescence intensity of erythrocyte membrane proteins. Read the rest here:
Mol Pharmacol. 2012 Jan 19; Breast cancer resistance protein (BCRP/ABCG2, an ATP-Binding Cassette (ABC) membrane-associated drug efflux transporter, is known to localize at the blood-brain barrier (BBB) and can significantly restrict xenobiotic permeability in the brain. The objective of this study is to investigate the regulation of BCRP functional expression by peroxisome proliferator-activated receptor alpha (PPARα), a ligand-activated transcription factor primarily involved in lipid metabolism, in a cerebral microvascular endothelial cell culture system (hCMEC/D3), representative of human BBB. We demonstrate that PPARα selective ligands (i.e., clofibrate, GW7647) significantly induce BCRP mRNA and protein expression in a time and concentration-dependent manner, while pharmacological inhibitors (i.e., MK886; GW6471) prevent this induction. Using [3H]-mitoxantrone, an established BCRP substrate, we observe a significant reduction in its cellular accumulation by monolayer cells treated with clofibrate suggesting increased BCRP efflux activity. Furthermore, we show a significant decrease in BCRP protein expression and function when PPARα is downregulated by small interfering RNA. Applying chromatin-immunoprecipitation and quantitative real-time PCR, we observe that clofibrate treatment increases PPARα binding to the peroxisome proliferator response element within ABCG2 gene promoter. This study provides the first evidence of direct BCRP regulation by PPARα in a human in vitro BBB model and suggests new targeting strategies for either improving drug brain bioavailability or increasing neuroprotection.
J Biol Chem. 2012 Jan 23; Alpha-dystroglycan (α-DG) is a membrane-associated glycoprotein that interacts with several extracellular matrix proteins, including laminin and agrin. Aberrant glycosylation of α-DG disrupts its interaction with ligands and causes a certain type of muscular dystrophy commonly referred to as dystroglycanopathy. It has been reported that a unique O-mannosyl tetrasaccharide (Neu5Ac-α2,3-Gal-β1,4-GlcNAc-β1,2-Man) and a phosphodiester-linked modification on O-mannose play important roles in the laminin binding activity of α-DG. In this study, we use several dystroglycanopathy mouse models to demonstrate that, in addition to fukutin and LARGE, fukutin-related protein (FKRP) is also involved in the post-phosphoryl modification of O-mannose on α-DG. Furthermore, we have found that the glycosylation status of α-DG in lung and testis is minimally affected by defects in fukutin, LARGE or FKRP. α-DG prepared from wild-type lung- or testis-derived cells lacks the post-phosphoryl moiety and shows little laminin-binding activity. These results show that FKRP is involved in post-phosphoryl modification rather than in O-mannosyl tetrasaccharide synthesis. Our data also demonstrate that post-phosphoryl modification not only plays critical roles in the pathogenesis of dystroglycanopathy but also is a key determinant of α-DG functional expression as a laminin receptor in normal tissues and cells. Read the original here:
Biol Reprod. 2012 Jan 11; Connexin expression and gap junctional intercellular communication (GJIC) mediated by CONNEXIN 43 (Cx43/GJA1) are required for cytotrophoblast fusion into the syncytium, the outer functional layer of the human placenta. Cx43 also impacts intracellular signaling through protein-protein interactions. The transcription factor GCM1 and its downstream target ERVW-1/SYNCYTIN-1 are key players in trophoblast fusion and exert their actions through the ERVW-1 receptor SLC1A5/ASCT-2/RDR/ATB(0). To investigate the molecular role of the Cx43 protein and its interaction with this fusogenic pathway we utilized stable Cx43 transfected cell lines established from the choriocarcinoma cell line Jeg3: (wild type), alphahCG/Cx43 (constitutive Cx43 expression); JpUHD/Cx43 (doxycyclin inducible Cx43 expression) or JpUHD/tr Cx43 (doxycyclin inducible Cx43 carboxyterminal deleted). We hypothesized that truncation of Cx43 at its C-terminus would inhibit trophoblast fusion and protein interaction with either ERVW-1 or SLC1A5. In the alphahCG/Cx43 and JpUHD/Cx43 lines stimulation with cAMP caused an; (1) increase in GJA1 mRNA levels, (2) increase in the percentage of fused cells and, (3) downregulation of SLC1A5 expression. Cell fusion was inhibited by GJIC blockade using Carbenoxylone. Neither Jeg3, which express low levels of Cx43, nor JpUHD/trCx43 cell lines demonstrated cell fusion or downregulation of SLC1A5. However, GCM1 and ERVW-1 mRNAs were upregulated by cAMP treatment in both Jeg3 and all Cx43 cell lines. Silencing of GCM1 prevented the induction of GJA1 mRNA by forskolin in BeWo choriocarcinoma cells, demonstrating that GCM1 is upstream of Cx43. All cell lines and first trimester villous explants also demonstrated co-immunoprecipitation of SLC1A5 and phosphorylated Cx43. Importantly SLC1A5 and Cx43 gap junction plaques colocalized in situ to areas of fusing cytotrophoblast demonstrated by the loss of E-cadherin staining in the plasma membrane in first trimester placenta. We conclude that Cx43 mediated GJIC and SLC1A5 interaction play important functional roles in trophoblast cell fusion. Read the original here:
PLoS One. 2012; 7(1): e29520 Multidrug resistance protein Pdr5p is a yeast ATP-binding cassette (ABC) transporter in the plasma membrane. It confers multidrug resistance by active efflux of intracellular drugs. However, the highly polymorphic Pdr5p from clinical strain YJM789 loses its ability to expel azole and cyclohexmide. To investigate the role of amino acid changes in this functional change, PDR5 chimeras were constructed by segmental replacement of homologous BY4741 PDR5 fragments. Functions of PDR5 chimeras were evaluated by fluconazole and cycloheximide resistance assays. Their expression, ATPase activity, and efflux efficiency for other substrates were also analyzed. Using multiple lines of evidence, we show that an alanine-to-methionine mutation at position 1352 located in the predicted short intracellular loop 4 significantly contributes to the observed transport deficiency. The degree of impairment is likely correlated to the size of the mutant residue. Go here to see the original:
PLoS One. 2012; 7(1): e29520 Multidrug resistance protein Pdr5p is a yeast ATP-binding cassette (ABC) transporter in the plasma membrane. It confers multidrug resistance by active efflux of intracellular drugs. However, the highly polymorphic Pdr5p from clinical strain YJM789 loses its ability to expel azole and cyclohexmide. To investigate the role of amino acid changes in this functional change, PDR5 chimeras were constructed by segmental replacement of homologous BY4741 PDR5 fragments. Functions of PDR5 chimeras were evaluated by fluconazole and cycloheximide resistance assays. Their expression, ATPase activity, and efflux efficiency for other substrates were also analyzed. Using multiple lines of evidence, we show that an alanine-to-methionine mutation at position 1352 located in the predicted short intracellular loop 4 significantly contributes to the observed transport deficiency. The degree of impairment is likely correlated to the size of the mutant residue. Read the original: |
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