Miribane Dërmaku-Sopjani, Selim Kolgeci, Sokol Abazi, Mentor Sopjani
{"title":"Significance of the anti-aging protein Klotho.","authors":"Miribane Dërmaku-Sopjani, Selim Kolgeci, Sokol Abazi, Mentor Sopjani","doi":"10.3109/09687688.2013.837518","DOIUrl":"https://doi.org/10.3109/09687688.2013.837518","url":null,"abstract":"<p><p>The Klotho gene was identified as an 'aging suppressor' in mice. Overexpression of the Klotho gene extends lifespan and defective Klotho results in rapid aging and early death. Both the membrane and secreted forms of Klotho have biological activity that include regulatory effects on general metabolism and a more specific effect on mineral metabolism that correlates with its effect on aging. Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also functions as a humoral factor that regulates cell survival and proliferation, vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a potential tumor suppressor. Moreover, Klotho protects against several pathogenic processes in a FGF23-independent manner. These processes include cancer metastasis, vascular calcification, and renal fibrosis. This review covers the recent advances in Klotho research and discusses novel Klotho-dependent mechanisms that are clinically relevant in aging and age-related diseases.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 8","pages":"369-85"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.837518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31806326","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}
Kelly-Ann Vere, Joanna L Richens, Jordan S Lane, Helen J Harris, James Duggan, Paul O'Shea
{"title":"Evidence for sodium metasilicate receptors on the human osteoblast cell surface; spatial localization and binding properties.","authors":"Kelly-Ann Vere, Joanna L Richens, Jordan S Lane, Helen J Harris, James Duggan, Paul O'Shea","doi":"10.3109/09687688.2013.843031","DOIUrl":"https://doi.org/10.3109/09687688.2013.843031","url":null,"abstract":"<p><p>We report details of the interaction of sodium metasilicate with osteoblast cellular membranes using Fluoresceinphosphatidylethanolamine (FPE) as a fluorescent indicator of membrane interactions. Fluorescence imaging studies of the FPE-based indicator system revealed areas of localized binding that would be consistent with the presence of a structure with 'receptor-like' properties. From these results, it seems unlikely that silica binds 'non-specifically' to the osteoblast surface. Moreover, the receptors are localized into membrane domains. Such regions of the cell membrane could well be structures such as 'rafts' or other such localized domains within the membrane. The binding profile of silica with the osteoblast cell surface takes place with all the characteristics of a receptor-mediated process best represented by a cooperativity (sigmoidal) binding model with a Hill coefficient of 3.6.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":" ","pages":"386-93"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.843031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40256318","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}
{"title":"Location and membrane sources for autophagosome formation - from ER-mitochondria contact sites to Golgi-endosome-derived carriers.","authors":"Shu Ning Chan, Bor Luen Tang","doi":"10.3109/09687688.2013.850178","DOIUrl":"https://doi.org/10.3109/09687688.2013.850178","url":null,"abstract":"<p><p>Recent advances have revealed much about the signaling events and molecular components associated with autophagy. Although it is clear that there are multiple points of intersection and connection between autophagy and known vesicular membrane transport processes between membrane compartments, autophagy is modulated by a distinct set of molecular components, and the autophagosome has a unique membrane composition. A key question that has yet to be resolved with regards to autophagosome formation is its membrane source. Various evidences have indicated that membranes from the endoplasmic reticulum (ER), mitochondria, Golgi, endosomes and the plasma membrane could all potentially act as a source of autophagosomal membrane in non-specialized macroautophagy. Recent investigations have generated advances in terms of the mitochondria's involvement in starvation-induced autophagy, and refined localization of autophagosome formation to ER-mitochondria contact sites. On the other hand, data accumulates on the delivery of membrane sources to the pre-autophagosome structure by Atg9-containing mobile carriers, which likely originated from the Golgi-endosome system. The answer to the question on the origin of membrane materials for autophagosome biogenesis awaits further reconciliation of these different findings.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":" ","pages":"394-402"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.850178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40280124","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}
{"title":"Impact of histidine residues on the transmembrane helices of viroporins.","authors":"Yan Wang, Sang Ho Park, Ye Tian, Stanley J Opella","doi":"10.3109/09687688.2013.842657","DOIUrl":"https://doi.org/10.3109/09687688.2013.842657","url":null,"abstract":"<p><p>Abstract The role of histidine in channel-forming transmembrane (TM) helices was investigated by comparing the TM helices from Virus protein 'u' (Vpu) and the M2 proton channel. Both proteins are members of the viroporin family of small membrane proteins that exhibit ion channel activity, and have a single TM helix that is capable of forming oligomers. The TM helices from both proteins have a conserved tryptophan towards the C-terminus. Previously, alanine 18 of Vpu was mutated to histidine in order to artificially introduce the same HXXXW motif that is central to the proton channel activity of M2. Interestingly, the mutated Vpu TM resulted in an increase in helix tilt angle of 11° in lipid bilayers compared to the wild-type Vpu TM. Here, we find the reverse, when histidine 37 of the HXXXW motif in M2 was mutated to alanine, it decreased the helix tilt by 10° from that of wild-type M2. The tilt change is independent of both the helix length and the presence of tryptophan. In addition, compared to wild-type M2, the H37A mutant displayed lowered sensitivity to proton concentration. We also found that the solvent accessibility of histidine-containing M2 is greater than without histidine. This suggests that the TM helix may increase the solvent exposure by changing its tilt angle in order to accommodate a polar/charged residue within the hydrophobic membrane region. The comparative results of M2, Vpu and their mutants demonstrated the significance of histidine in a transmembrane helix and the remarkable plasticity of the function and structure of ion channels stemming from changes at a single amino acid site. </p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 7","pages":"360-9"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.842657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31787242","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}
{"title":"Lipase activity in lipidomics - a hidden problem?","authors":"Samuel Furse, J Antoinette Killian","doi":"10.3109/09687688.2013.835125","DOIUrl":"https://doi.org/10.3109/09687688.2013.835125","url":null,"abstract":"A perennial problem in ‘omics’ studies, is ensuring that the molecular profile produced is a true representation of that in the system from which it comes. Scientists working in the field of proteomics, still the most advanced ‘omics’ discipline, have for some time recognized the potential of proteases to interfere with the results they obtain (Lopez-Otin and Overall 2002). This remains prescient with the advent of quantitative proteomics. It comes as no surprise, therefore, that protease inhibitors have been standard in proteomics research for some years and that for much of this time, convenient catch-all small-molecule inhibitor packages have been commercially available.","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":" ","pages":"347-9"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.835125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40254623","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}
{"title":"Getting into the cilia: nature of the barrier(s).","authors":"Yi Shan Lim, Bor Luen Tang","doi":"10.3109/09687688.2013.842003","DOIUrl":"https://doi.org/10.3109/09687688.2013.842003","url":null,"abstract":"<p><p>The primary cilium that protrudes from the plasma membrane of many eukaryotic cell types is very much a cellular organelle in its own right. Its unique membrane and luminal composition is effectively compartmentalized by diffusion barrier at its base, known as the transition zone. Recent works have now shed light on the molecular components of this diffusion barrier, and revealed intriguing functional similarities with other better characterized cellular barriers.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 7","pages":"350-4"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.842003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31785640","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}
{"title":"How do transporters couple solute movements?","authors":"Gary Rudnick","doi":"10.3109/09687688.2013.842658","DOIUrl":"https://doi.org/10.3109/09687688.2013.842658","url":null,"abstract":"<p><p>Abstract The availability of high-resolution atomic structures for transport proteins provides unprecedented opportunities for understanding their mechanism of action. The details of conformational change can be deduced from these structures, especially when multiple conformations are available. However, the singular ability of transporters to couple the movement of one solute to that of another requires even more information than what is supplied by a crystal structure. This short commentary discusses how recent biochemical and biophysical studies are beginning to reveal how solute coupling is achieved. </p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":" ","pages":"355-9"},"PeriodicalIF":0.0,"publicationDate":"2013-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.842658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40256173","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}
Semen O Yesylevskyy, Sebastian Kraszewski, Fabien Picaud, Christophe Ramseyer
{"title":"Efficiency of the monofunctionalized C60 fullerenes as membrane targeting agents studied by all-atom molecular dynamics simulations.","authors":"Semen O Yesylevskyy, Sebastian Kraszewski, Fabien Picaud, Christophe Ramseyer","doi":"10.3109/09687688.2013.828856","DOIUrl":"https://doi.org/10.3109/09687688.2013.828856","url":null,"abstract":"<p><p>Transmembrane translocation of C60 fullerenes functionalized by the single amino-derivative in neutral and charged forms was studies by extensive all-atom molecular dynamics simulations. It is shown that these complexes exhibit very strong affinity to the membrane core, but their spontaneous translocation through the membrane is not possible at practical time scale. In contrast, free amino derivatives translocate through the membrane much easier than their complexes with fullerenes, but do not have pronounced affinity to the membrane interior. Our results suggest that monofunctionalized C60 could be extremely efficient membrane targeting agents, which facilitate accumulation of the water-soluble compounds in the hydrophobic core of lipid bilayer.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 5-6","pages":"338-45"},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.828856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31673901","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}
{"title":"Expression, characterization and ligand specificity of lipocalin-1 interacting membrane receptor (LIMR).","authors":"Renske W Hesselink, John B C Findlay","doi":"10.3109/09687688.2013.823018","DOIUrl":"https://doi.org/10.3109/09687688.2013.823018","url":null,"abstract":"<p><p>Human lipocalin-1 interacting membrane receptor (LIMR) was the first lipocalin receptor to be identified, as a specific receptor for lipocalin-1 (Lcn1). Subsequently LIMR has been reported to interact with other ligands as well, notably with the bovine lipocalin β-lactoglobulin (BLG) and with the unrelated secretoglobin uteroglobin (UG). To study the ligand-binding behaviour of this prototypic lipocalin receptor in more detail, a system was developed for the recombinant expression of LIMR in Drosophila Schneider 2 (S2) cells, and for the subsequent solubilization and purification of the protein. The receptor forms dimers or larger oligomers when solubilized in n-dodecyl β-D-maltoside (DDM). The full-length, functional receptor was captured onto a surface plasmon resonance (SPR) chip via an α-V5 antibody, and the binding of various potential ligands was followed in time. In this way, LIMR was shown to be highly specific for Lcn1, binding the lipocalin with low micromolar to high nanomolar affinity. No interactions with any of the other putative ligands could be detected, raising doubts about the physiological relevance of the reported binding of BLG and UG to the receptor.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 5-6","pages":"327-37"},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.823018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31673487","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}
Abdallah Fallah, Rachel Pierre, Elie Abed, Robert Moreau
{"title":"Lysophosphatidylcholine-induced cytotoxicity in osteoblast-like MG-63 cells: involvement of transient receptor potential vanilloid 2 (TRPV2) channels.","authors":"Abdallah Fallah, Rachel Pierre, Elie Abed, Robert Moreau","doi":"10.3109/09687688.2013.828855","DOIUrl":"https://doi.org/10.3109/09687688.2013.828855","url":null,"abstract":"<p><p>Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Accordingly, atherogenic determinants such as oxidized low density lipoprotein (OxLDL) particles have been shown to alter bone cell functions. In this work, we investigated the cytotoxicity of lysophosphatidylcholine (lysoPC), a major phospholipid component generated upon LDL oxidation, on bone-forming MG-63 osteoblast-like cells. Cell viability was reduced by lysoPC in a concentration-dependent manner with a LC50 of 18.7±0.7 μM. LysoPC-induced cell death was attributed to induction of both apoptosis and necrosis. Since impairment of intracellular calcium homeostasis is often involved in mechanism of cell death, we determined the involvement of calcium in lysoPC-induced cytotoxicity. LysoPC promoted a rapid and transient increase in intracellular calcium attributed to mobilization from calcium stores, followed by a sustained influx. Intracellular calcium mobilization was associated to phospholipase C (PLC)-dependent mobilization of calcium from the endoplasmic reticulum since inhibition of PLC or calcium depletion of reticulum endoplasmic with thapsigargin prevented the calcium mobilization. The calcium influx induced by lysoPC was abolished by inhibition of transient receptor potential vanilloid (TRPV) channels with ruthenium red whereas gadolinium, which inhibits canonical TRP (TRPC) channels, was without effect. Accordingly, expression of TRPV2 and TRPV4 were shown in MG-63 cells. The addition of TRPV2 inhibitor Tranilast in the incubation medium prevent the calcium influx triggered by lysoPC and reduced lysoPC-induced cytotoxicity whereas TRPV4 inhibitor RN 1734 was without effect, which confirms the involvement of TRPV2 activation in lysoPC-induced cell death.</p>","PeriodicalId":18858,"journal":{"name":"Molecular Membrane Biology","volume":"30 5-6","pages":"315-26"},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/09687688.2013.828855","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31673488","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}