Journal of Membrane Biology最新文献

Early Events in β₂AR Dimer Dynamics Mediated by Activation-Related Microswitches. 激活相关微开关介导的 β2AR 二聚体动力学早期事件

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-09-06 DOI: 10.1007/s00232-024-00324-1

Aneesh Kotipalli, Shruti Koulgi, Vinod Jani, Uddhavesh Sonavane, Rajendra Joshi

{"title":"Early Events in β2AR Dimer Dynamics Mediated by Activation-Related Microswitches.","authors":"Aneesh Kotipalli, Shruti Koulgi, Vinod Jani, Uddhavesh Sonavane, Rajendra Joshi","doi":"10.1007/s00232-024-00324-1","DOIUrl":"https://doi.org/10.1007/s00232-024-00324-1","url":null,"abstract":"G-Protein-Coupled Receptors (GPCRs) make up around 3-4% of the human genome and are the targets of one-third of FDA-approved drugs. GPCRs typically exist as monomers but also aggregate to form higher-order oligomers, including dimers. β2AR, a pharmacologically relevant GPCR, is known to be targeted for the treatment of asthma and cardiovascular diseases. The activation of β2AR at the dimer level remains under-explored. In the current study, molecular dynamics (MD) simulations have been performed to understand activation-related structural changes in β2AR at the dimer level. The transition from inactive to active and vice versa has been studied by starting the simulations in the apo, agonist-bound, and inverse agonist-bound β2AR dimers for PDB ID: 2RH1 and PDB ID: 3P0G, respectively. A cumulative total of around 21-μs simulations were performed. Residue-based distances, RMSD, and PCA calculations suggested that either of the one monomer attained activation-related features for the apo and agonist-bound β2AR dimers. The TM5 and TM6 helices within the two monomers were observed to be in significant variation in all the simulations. TM5 bulge and proximity of TM2 and TM7 helices may be contributing to one of the early events in activation. The dimeric interface between TM1 and helix 8 were observed to be well maintained in the apo and agonist-bound simulations. The presence of inverse agonists favored inactive features in both the monomers. These key features of activation known for monomers were observed to have an impact on β2AR dimers, thereby providing an insight into the oligomerization mechanism of GPCRs.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies. 生物电膜电位的演变：癌症发病机制和治疗策略的意义

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-25 DOI: 10.1007/s00232-024-00323-2

Anju Shrivastava, Amit Kumar, Lalit Mohan Aggarwal, Satyajit Pradhan, Sunil Choudhary, Ashish Ashish, Keshav Kashyap, Shivani Mishra

{"title":"Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.","authors":"Anju Shrivastava, Amit Kumar, Lalit Mohan Aggarwal, Satyajit Pradhan, Sunil Choudhary, Ashish Ashish, Keshav Kashyap, Shivani Mishra","doi":"10.1007/s00232-024-00323-2","DOIUrl":"https://doi.org/10.1007/s00232-024-00323-2","url":null,"abstract":"Electrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders. TRPM8在脂质-水-界面上的残基与胆固醇相互作用共同进化，并与多种健康疾病相关。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-16 DOI: 10.1007/s00232-024-00319-y

Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami

引用次数: 0

A Model for Reversible Electroporation to Deliver Drugs into Diseased Tissues. 向病变组织输送药物的可逆电穿孔模型

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-12 DOI: 10.1007/s00232-024-00321-4

Nilay Mondal, D C Dalal

{"title":"A Model for Reversible Electroporation to Deliver Drugs into Diseased Tissues.","authors":"Nilay Mondal, D C Dalal","doi":"10.1007/s00232-024-00321-4","DOIUrl":"https://doi.org/10.1007/s00232-024-00321-4","url":null,"abstract":"Drug delivery through electroporation could be highly beneficial for the treatment of different types of diseased tissues within the human body. In this work, a mathematical model of reversible tissue electroporation is presented for injecting drug into the diseased cells. The model emphasizes the tissue boundary where the drug is injected as a point source. In addition, the effect of drug loss at tissue boundaries through extracellular space is studied elaborately. Multiple pulses are applied to deliver a sufficient amount of drug into the targeted cells. The set of differential equations that model the physical circumstances are solved numerically. This model obtains a mass transfer coefficient (MTC), in terms of pore fraction coefficient and drug permeability that controls the drug transport from extracellular to intracellular space. The drug penetration throughout the tissue is captured for the application of different pulses. The boundary effects on drug concentration are highlighted in this study. The advocated model is able to perform homogeneous drug transport into the cells so that the affected tissue is treated completely. This model can be applied to optimize clinical experiments by avoiding the lengthy and costly in vivo and in vitro experiments.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Feasibility Study for the Use of Gene Electrotransfer and Cell Electrofusion as a Single-Step Technique for the Generation of Activated Cancer Cell Vaccines. 将基因电转移和细胞电融合作为一步法生成活化癌细胞疫苗的可行性研究》。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-12 DOI: 10.1007/s00232-024-00320-5

Marko Ušaj, Mojca Pavlin, Maša Kandušer

{"title":"Feasibility Study for the Use of Gene Electrotransfer and Cell Electrofusion as a Single-Step Technique for the Generation of Activated Cancer Cell Vaccines.","authors":"Marko Ušaj, Mojca Pavlin, Maša Kandušer","doi":"10.1007/s00232-024-00320-5","DOIUrl":"https://doi.org/10.1007/s00232-024-00320-5","url":null,"abstract":"Cell-based therapies hold great potential for cancer immunotherapy. This approach is based on manipulation of dendritic cells to activate immune system against specific cancer antigens. For the development of an effective cell vaccine platform, gene transfer, and cell fusion have been used for modification of dendritic or tumor cells to express immune (co)stimulatory signals and to load dendritic cells with tumor antigens. Both, gene transfer and cell fusion can be achieved by single technique, a cell membrane electroporation. The cell membrane exposed to external electric field becomes temporarily permeable, enabling introduction of genetic material, and also fusogenic, enabling the fusion of cells in the close contact. We tested the feasability of combining gene electrotransfer and electrofusion into a single-step technique and evaluated the effects of electroporation buffer, pulse parameters, and cell membrane fluidity for single or combined method of gene delivery or cell fusdion. We determined the percentage of fused cells expressing green fluorescence protein (GFP) in a murine cell model of melanoma B16F1, cell line used in our previous studies. Our results suggest that gene electrotransfer and cell electrofusion can be applied in a single step. The percentage of viable hybrid cells expressing GFP depends on electric pulse parameters and the composition of the electroporation buffer. Furthermore, our results suggest that cell membrane fluidity is not related to the efficiency of the gene electrotransfer and electrofusion. The protocol is compatible with microfluidic devices, however further optimization of electric pulse parameters and buffers is still needed.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs. 蝎子毒液中短抗菌肽及其理化特性和新药开发潜力的重要综述》。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-01 Epub Date: 2024-07-11 DOI: 10.1007/s00232-024-00315-2

Pedro Alejandro Fong-Coronado, Verónica Ramirez, Verónica Quintero-Hernández, Daniel Balleza

{"title":"A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs.","authors":"Pedro Alejandro Fong-Coronado, Verónica Ramirez, Verónica Quintero-Hernández, Daniel Balleza","doi":"10.1007/s00232-024-00315-2","DOIUrl":"10.1007/s00232-024-00315-2","url":null,"abstract":"Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aggregation Behavior of Amyloid Beta Peptide Depends Upon the Membrane Lipid Composition. 淀粉样β肽的聚集行为取决于膜脂质成分

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI: 10.1007/s00232-024-00314-3

Lipika Mirdha

引用次数: 0

Sperm-Specific CatSper is Not Conserved in All Vertebrates and May Not be the Only Progesterone-Responsive Ion Channel Present in Sperm. 精子特异性 CatSper 并非在所有脊椎动物中都是保守的，也可能不是精子中唯一的孕酮反应性离子通道。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-01 Epub Date: 2024-07-06 DOI: 10.1007/s00232-024-00316-1

Nishant Kumar Dubey, Vikash Kumar, Chandan Goswami

{"title":"Sperm-Specific CatSper is Not Conserved in All Vertebrates and May Not be the Only Progesterone-Responsive Ion Channel Present in Sperm.","authors":"Nishant Kumar Dubey, Vikash Kumar, Chandan Goswami","doi":"10.1007/s00232-024-00316-1","DOIUrl":"10.1007/s00232-024-00316-1","url":null,"abstract":"Progesterone (P4) acts as a key conserved signalling molecule in vertebrate reproduction. P4 is especially important for mature sperm physiology and subsequent reproductive success. \"CatSpermasome\", a multi-unit molecular complex, has been suggested to be the main if not the only P4-responsive atypical Ca2+-ion channel present in mature sperm. Altogether, here we analyse the protein sequences of CatSper1-4 from more than 500 vertebrates ranging from early fishes to humans. CatSper1 becomes longer in mammals due to sequence gain mainly at the N-terminus. Overall the conservation of full-length CatSper1-4 as well as the individual TM regions remain low. The lipid-water-interface residues (i.e. a 5 amino acid stretch sequence present on both sides of each TM region) also remain highly diverged. No specific patterns of amino acid distributions were observed. The total frequency of positively charged, negatively charged or their ratios do not follow in any specific pattern. Similarly, the frequency of total hydrophobic, total hydrophilic residues or even their ratios remain random and do not follow any specific pattern. We noted that the CatSper1-4 genes are missing in amphibians and the CatSper1 gene is missing in birds. The high variability of CatSper1-4 and gene-loss in certain clades indicate that the \"CatSpermasome\" is not the only P4-responsive ion channel. Data indicate that the molecular evolution of CatSper is mostly guided by diverse hydrophobic ligands rather than only P4. The comparative data also suggest possibilities of other Ca2+-channel/s in vertebrate sperm that can also respond to P4.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N-Glycosylation Deficiency in Transgene α7 nAChR and RIC3 Expressing CHO Cells Without NACHO. 无 NACHO 的转基因 α7 nAChR 和 RIC3 表达 CHO 细胞中的 N-糖基化缺陷。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.1007/s00232-024-00317-0

Sabrina Brockmöller, Lara Maria Molitor, Thomas Seeger, Franz Worek, Simone Rothmiller

{"title":"N-Glycosylation Deficiency in Transgene α7 nAChR and RIC3 Expressing CHO Cells Without NACHO.","authors":"Sabrina Brockmöller, Lara Maria Molitor, Thomas Seeger, Franz Worek, Simone Rothmiller","doi":"10.1007/s00232-024-00317-0","DOIUrl":"10.1007/s00232-024-00317-0","url":null,"abstract":"The human neuronal nicotinic acetylcholine receptor α7 (nAChR) is an important target implicated in diseases like Alzheimer's or Parkinson's, as well as a validated target for drug discovery. For α7 nAChR model systems, correct folding and ion influx functions are essential. Two chaperones, resistance to inhibitors of cholinesterase 3 (RIC3) and novel nAChR regulator (NACHO), enhance the assembly and function of α7 nAChR. This study investigates the consequence of NACHO absence on α7 nAChR expression and function. Therefore, the sequences of human α7 nAChR and human RIC3 were transduced in Chinese hamster ovary (CHO) cells. Protein expression and function of α7 nAChR were confirmed by Western blot and voltage clamp, respectively. Cellular viability was assessed by cell proliferation and lactate dehydrogenase assays. Intracellular and extracellular expression were determined by in/on-cell Western, compared with another nAChR subtype by novel cluster fluorescence-linked immunosorbent assay, and N-glycosylation efficiency was assessed by glycosylation digest. The transgene CHO cell line showed expected protein expression and function for α7 nAChR and cell viability was barely influenced by overexpression. While intracellular levels of α7 nAChR were as anticipated, plasma membrane insertion was low. The glycosylation digest revealed no appreciable N-glycosylation product. This study demonstrates a stable and functional cell line expressing α7 nAChR, whose protein expression, function, and viability are not affected by the absence of NACHO. The reduced plasma membrane insertion of α7 nAChR, combined with incorrect matured N-glycosylation at the Golgi apparatus, suggests a loss of recognition signal for lectin sorting.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correlation Between Antimicrobial Structural Classes and Membrane Partitioning: Role of Emerging Lipid Packing Defects. 抗菌剂结构类别与膜分离之间的相关性：新出现的脂质包装缺陷的作用。

IF 2.3 4区生物学

Journal of Membrane Biology Pub Date : 2024-07-22 DOI: 10.1007/s00232-024-00318-z

S V Sankaran, Roni Saiba, Samapan Sikdar, Satyavani Vemparala

{"title":"Correlation Between Antimicrobial Structural Classes and Membrane Partitioning: Role of Emerging Lipid Packing Defects.","authors":"S V Sankaran, Roni Saiba, Samapan Sikdar, Satyavani Vemparala","doi":"10.1007/s00232-024-00318-z","DOIUrl":"https://doi.org/10.1007/s00232-024-00318-z","url":null,"abstract":"In this study, a combination of bioinformatics and molecular dynamics simulations is employed to investigate the partitioning behavior of different classes of antimicrobial peptides (AMPs) into model membranes. The main objective is to identify any correlations between the structural characteristics of AMPs and their membrane identification and early-stage partitioning mechanisms. The simulation results reveal distinct membrane interactions among the various structural classes of AMPs, particularly in relation to the generation and subsequent interaction with lipid packing defects. Notably, AMPs with a structure-less coil conformation generate a higher number of deep and shallow defects, which are larger in size compared to other classes of AMPs. AMPs with helical component demonstrated the deepest insertion into the membrane. On the other hand, AMPs with a significant percentage of beta sheets tend to adsorb onto the membrane surface, suggesting a potentially distinct partitioning mechanism attributed to their structural rigidity. These findings highlight the diverse membrane interactions and partitioning mechanisms exhibited by different structural classes of AMPs.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0