Molecular Membrane Biology最新文献_第5页

A Tribute to Stephen Allan Baldwin. 致敬斯蒂芬·艾伦·鲍德温。

Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-06-22 DOI: 10.3109/09687688.2015.1031834

Tony Magee, Peter Henderson, Alison Baker, Vincent Postis, Stephen Muench

引用次数: 0

The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1. 多药耐药泵ABCB1是泛素连接酶NEDD4-1的底物。

Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-05-26 DOI: 10.3109/09687688.2015.1023378

Begum G Akkaya, Joseph K Zolnerciks, Tasha K Ritchie, Bjoern Bauer, Anika M S Hartz, James A Sullivan, Kenneth J Linton

{"title":"The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1.","authors":"Begum G Akkaya, Joseph K Zolnerciks, Tasha K Ritchie, Bjoern Bauer, Anika M S Hartz, James A Sullivan, Kenneth J Linton","doi":"10.3109/09687688.2015.1023378","DOIUrl":"https://doi.org/10.3109/09687688.2015.1023378","url":null,"abstract":"Abstract The ATP Binding Cassette transporter ABCB1 can export the neurotoxic peptide β-amyloid from endothelial cells that line the blood-brain barrier (BBB). This has the potential to lower cerebral levels of β-amyloid, but ABCB1 expression in the BBB appears to be progressively reduced in patients with Alzheimer’s disease. The surface density of many membrane proteins is regulated by ubiquitination catalyzed by ubiquitin E3 ligases. In brain capillaries of mice challenged with β-amyloid ex vivo, we show that the level of the ubiquitin ligase Nedd4 increases concomitant with reduction in Abcb1. In vitro we show that human ABCB1 is a substrate for human NEDD4-1 ligase. Recombinant ABCB1 was purified from Sf21 insect cells and incubated with recombinant NEDD4-1 purified from Escherichia coli. The treated ABCB1 had reduced mobility on SDS-PAGE, and mass spectrometry identified eight lysine residues, K271, K272, K575, K685, K877, K885, K887 and K1062 that were ubiquitinated by NEDD4-1. Molecular modelling showed that all of the residues are exposed on the surface of the intracellular domains of ABCB1. K877, K885 and K887 in particular, are located in the intracellular loop of transmembrane helix 10 (TMH10) in close proximity, in the tertiary fold, to a putative NEDD4-1 binding site in the intracellular helix extending from TMH12 (PxY motif, residues 996–998). Transient expression of NEDD4-1 in HEK293 Flp-In cells stably expressing ABCB1 was shown to reduce the surface density of the transporter. Together, the data identify this ubiquitin ligase as a potential target for intervention in the pathophysiology of Alzheimer’s disease.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"32 2","pages":"39-45"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2015.1023378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33211081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Emerging roles of system [Formula: see text] antiporter and its inhibition in CNS disorders. 系统的新角色[公式:见文本]逆向转运蛋白及其在中枢神经系统疾病中的抑制作用。

Molecular Membrane Biology Pub Date : 2015-01-01 DOI: 10.3109/09687688.2015.1096972

Dhaval Patel, Prashant S Kharkar, Mukesh Nandave

{"title":"Emerging roles of system [Formula: see text] antiporter and its inhibition in CNS disorders.","authors":"Dhaval Patel, Prashant S Kharkar, Mukesh Nandave","doi":"10.3109/09687688.2015.1096972","DOIUrl":"https://doi.org/10.3109/09687688.2015.1096972","url":null,"abstract":"System [Formula: see text] is an antiporter belonging to the hetero(di)meric amino acid transporter family. It is located on astrocytes as well as on blood-brain barrier within the CNS. It plays a pivotal role in free radical neutralization as well as neuronal signalling by regulating the glutathione production which occurs via the exchange of intracellular glutamate with extracellular cystine at 1:1 molar ratio. Understandably, it is a vital component responsible for the maintenance of neuronal homeostasis (e.g. redox state). Hence, it could be postulated that any perturbation in system [Formula: see text] function may contribute, directly or indirectly, to the pathophysiology of a variety of CNS disorders like Alzheimer's disease, schizophrenia, drug addiction, depression, multiple sclerosis, hypoglycemic neuronal cell death, glioma, and excitotoxicity, making system [Formula: see text] a promising target for treating CNS disorders. In recent times, recognizing the potential of this target, variety of inhibitors has been synthesized by modifying commercially available potent inhibitors including sulfasalazine, erastin, and sorafenib. Although, they have demonstrated efficacy, the in-depth data is still lacking to warrant their use for the treatment of aforementioned CNS disorders. In this review, we discuss the in-depth role of system [Formula: see text] transporter in maintaining normal physiology as well as in the pathophysiology of CNS diseases. Additionally, we have also listed some of the potent inhibitors of system [Formula: see text]. In conclusion, the critical role of system [Formula: see text] in multiple CNS disorders and advanced research on its inhibitors have promising future prospects for better management of the CNS ailments.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"32 4","pages":"89-116"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2015.1096972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34121940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Sonic hedgehog multimerization: a self-organizing event driven by post-translational modifications? 音速刺猬多聚化：翻译后修饰驱动的自组织事件？

Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-08-27 DOI: 10.3109/09687688.2015.1066895

Mirella V Koleva, Stephen Rothery, Martin Spitaler, Mark A A Neil, Anthony I Magee

{"title":"Sonic hedgehog multimerization: a self-organizing event driven by post-translational modifications?","authors":"Mirella V Koleva, Stephen Rothery, Martin Spitaler, Mark A A Neil, Anthony I Magee","doi":"10.3109/09687688.2015.1066895","DOIUrl":"10.3109/09687688.2015.1066895","url":null,"abstract":"Sonic hedgehog (Shh) is a morphogen active during vertebrate development and tissue homeostasis in adulthood. Dysregulation of the Shh signalling pathway is known to incite carcinogenesis. Due to the highly lipophilic nature of this protein imparted by two post-translational modifications, Shh's method of transit through the aqueous extracellular milieu has been a long-standing conundrum, prompting the proposition of numerous hypotheses to explain the manner of its displacement from the surface of the producing cell. Detection of high molecular-weight complexes of Shh in the intercellular environment has indicated that the protein achieves this by accumulating into multimeric structures prior to release from producing cells. The mechanism of assembly of the multimers, however, has hitherto remained mysterious and contentious. Here, with the aid of high-resolution optical imaging and post-translational modification mutants of Shh, we show that the C-terminal cholesterol and the N-terminal palmitate adducts contribute to the assembly of large multimers and regulate their shape. Moreover, we show that small Shh multimers are produced in the absence of any lipid modifications. Based on an assessment of the distribution of various dimensional characteristics of individual Shh clusters, in parallel with deductions about the kinetics of release of the protein from the producing cells, we conclude that multimerization is driven by self-assembly underpinned by the law of mass action. We speculate that the lipid modifications augment the size of the multimolecular complexes through prolonging their association with the exoplasmic membrane.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"32 3","pages":"65-74"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33955432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphatidylcholine's functions beyond that of a membrane brick. 磷脂酰胆碱的功能超出了膜砖的功能。

Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-08-25 DOI: 10.3109/09687688.2015.1066894

Samuel Furse, Anton I P M de Kroon

引用次数: 90

Isolation of lipids from biological samples. 从生物样品中分离脂质。

Molecular Membrane Biology Pub Date : 2015-01-01 Epub Date: 2015-07-27 DOI: 10.3109/09687688.2015.1050468

Samuel Furse, Maarten R Egmond, J Antoinette Killian

引用次数: 34

The arginine-facing amino acid residue of the rat aquaporin 1 constriction determines solute selectivity according to its size and lipophilicity. 大鼠水通道蛋白1缩窄的精氨酸面氨基酸残基根据其大小和亲脂性决定溶质选择性。

Molecular Membrane Biology Pub Date : 2014-11-01 Epub Date: 2014-10-24 DOI: 10.3109/09687688.2014.960493

Dawid Krenc, Jie Song, Abdulnasser Almasalmeh, Binghua Wu, Eric Beitz

{"title":"The arginine-facing amino acid residue of the rat aquaporin 1 constriction determines solute selectivity according to its size and lipophilicity.","authors":"Dawid Krenc, Jie Song, Abdulnasser Almasalmeh, Binghua Wu, Eric Beitz","doi":"10.3109/09687688.2014.960493","DOIUrl":"https://doi.org/10.3109/09687688.2014.960493","url":null,"abstract":"Aquaporins (AQP) are transmembrane channels for small, predominantly uncharged solutes. Their selectivity is partly determined by the aromatic/arginine constriction. Ammonia is similar in size and polarity to water, yet a subset of aquaporins distinguishes between the two. We mutated the constriction of water-selective rat AQP1 to mimic that of the ammonia-permeable human AQP8 by replacing Phenylalanine 56 with histidine, Histidine 180 with isoleucine, and Cysteine 189 with glycine, alone and in combination. Only AQP1 mutants including the H180I exchange increased the ammonia and methylamine tolerance of yeast. In a second set of mutations, we replaced Histidine 180 with alanine, leucine, methionine, phenylalanine, asparagine or glutamine. AQP1 H180A was equivalent to AQP1 H180I. AQP1 H180L increased ammonia but not methylamine tolerance of yeast. AQP1 mutants with methionine, phenylalanine, asparagine or glutamine in place of Histidine 180, increased neither ammonia nor methylamine tolerance of yeast. All mutants conducted water, as judged by osmotic assays with yeast sphaeroplasts. We propose that the arginine-facing amino acid residue is the most versatile selector of aquaporin constrictions, excluding Escherichia coli glycerol facilitator-type aquaporins.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"31 7-8","pages":"228-38"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2014.960493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32767990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Cholesterol modulates the interaction of the islet amyloid polypeptide with membranes. 胆固醇调节胰岛淀粉样多肽与细胞膜的相互作用。

Molecular Membrane Biology Pub Date : 2014-11-01 Epub Date: 2014-12-15 DOI: 10.3109/09687688.2014.987182

Lucie Caillon, Luminita Duma, Olivier Lequin, Lucie Khemtemourian

{"title":"Cholesterol modulates the interaction of the islet amyloid polypeptide with membranes.","authors":"Lucie Caillon, Luminita Duma, Olivier Lequin, Lucie Khemtemourian","doi":"10.3109/09687688.2014.987182","DOIUrl":"https://doi.org/10.3109/09687688.2014.987182","url":null,"abstract":"The deposition of insoluble amyloid fibrils resulting from the aggregation of the human islet amyloid polypeptide (hIAPP) within the islet of Langerhans is a pathological feature of type 2 diabetes mellitus (T2DM). Increasing evidence indicates that biological membranes play a key role in amyloid aggregation, modulating among others the kinetics of amyloid formation, and being the target of toxic species generated during amyloid formation. In T2DM patients, elevated levels of cholesterol, an important determinant of the physical state of biological membranes, are observed in β-cells and are thought to directly impair β-cell function and insulin secretion. However, it is not known whether cholesterol enhances membrane-interaction or membrane-insertion of hIAPP. In this study, we investigated the effect of cholesterol incorporated in zwitterionic and anionic membranes. Our circular dichroism and liquid state NMR data reveal that 10-30% of cholesterol slightly affects the aggregational and conformational behaviour of hIAPP. Additional fluorescence results indicate that 10 and 20% of cholesterol slightly slow down the kinetics of oligomer and fibril formation while anionic lipids accelerate this kinetics. This behavior might be caused by differences in membrane insertion and therefore in membrane binding of hIAPP. The membrane binding affinity was evaluated using (1)H NMR experiments and our results show that the affinity of hIAPP for membranes containing cholesterol is significantly smaller than that for membranes containing anionic lipids. Furthermore, we found that hIAPP-induced membrane damage is synchronized to fibril formation in the absence and in the presence of cholesterol.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"31 7-8","pages":"239-49"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2014.987182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32897079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Differential roles of tryptophan residues in the functional expression of human anion exchanger 1 (AE1, Band 3, SLC4A1). 色氨酸残基在人阴离子交换器1 (AE1, Band 3, SLC4A1)功能表达中的差异作用。

Molecular Membrane Biology Pub Date : 2014-11-01 Epub Date: 2014-09-26 DOI: 10.3109/09687688.2014.955829

Yuka Okawa, Jing Li, Arghya Basu, Joseph R Casey, Reinhart A F Reithmeier

{"title":"Differential roles of tryptophan residues in the functional expression of human anion exchanger 1 (AE1, Band 3, SLC4A1).","authors":"Yuka Okawa, Jing Li, Arghya Basu, Joseph R Casey, Reinhart A F Reithmeier","doi":"10.3109/09687688.2014.955829","DOIUrl":"https://doi.org/10.3109/09687688.2014.955829","url":null,"abstract":"Anion exchanger 1 (AE1) is a 95 kDa glycoprotein that facilitates Cl(-)=HCO(-)(3) exchange across the erythrocyte plasma membrane. This transport activity resides in the 52 kDa C-terminal membrane domain (Gly(361)-Val(911)) predicted to span the membrane 14 times. To explore the role of tryptophan (Trp) residues in AE1 function, the seven endogenous Trp residues in the membrane domain were mutated individually to alanine (Ala) and phenylalanine (Phe). Expression levels, cell surface abundance, inhibitor binding and transport activities of the mutants were measured upon expression in HEK-293 cells. The seven Trp residues divided into three classes according the impact of mutations on the functional expression of AE1: Class 1, dramatically decreased expression (Trp(492) and Trp(496)); Class 2, decreased expression by Ala substitution but not Phe (Trp(648), Trp(662) and Trp(723)); and Class 3, normal expression (Trp(831) and Trp(848)). The results indicate that Trp residues play differential roles in AE1 expression and function depending on their location in the protein and that Trp mutants with low expression are misfolded and retained in the endoplasmic reticulum.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"31 7-8","pages":"211-27"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2014.955829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32696871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Pyruvate dehydrogenase complex (PDC) export from the mitochondrial matrix. 丙酮酸脱氢酶复合物(PDC)从线粒体基质出口。

Molecular Membrane Biology Pub Date : 2014-11-01 Epub Date: 2014-12-15 DOI: 10.3109/09687688.2014.987183

Fanny Ng, Bor Luen Tang

引用次数: 21