{"title":"Aggregation Behavior of Amyloid Beta Peptide Depends Upon the Membrane Lipid Composition.","authors":"Lipika Mirdha","doi":"10.1007/s00232-024-00314-3","DOIUrl":"10.1007/s00232-024-00314-3","url":null,"abstract":"<p><p>Protein aggregation plays a crucial role in the development of several neurodegenerative diseases. It is important to understand the aggregation process for the detection of the onset of these diseases. Alzheimer's Disease (AD) is one of the most prevalent neurodegenerative diseases caused by the aggregation of Aβ-40 and Aβ-42 peptides. The smaller oligomers lead to the formation of protein plaque at the neural membranes leading to memory loss and other disorders. Interestingly, aggregation takes place at the neural membranes, therefore the membrane composition seems to play an important role in the aggregation process. Despite a large number of literatures on the effect of lipid composition on protein aggregation, there are very few concise reviews that highlight the role of membrane composition in protein aggregation. In this review, we have discussed the implication of membrane composition on the aggregation of amyloid beta peptide with a special emphasis on cholesterol. We have further discussed the role of the degree of unsaturation of fatty acids and the participation of apolipoprotein E4 (ApoE4) in the onset of AD.</p>","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":"141421658","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}
{"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":"<p><p>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 Ca<sup>2+</sup>-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 Ca<sup>2+</sup>-channel/s in vertebrate sperm that can also respond to P4.</p>","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}
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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
Catherine Carvajal, Jiajie Yan, Alma Nani, Jaime DeSantiago, Xiaoping Wan, Isabelle Deschenes, Xun Ai, Michael Fill
{"title":"Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.","authors":"Catherine Carvajal, Jiajie Yan, Alma Nani, Jaime DeSantiago, Xiaoping Wan, Isabelle Deschenes, Xun Ai, Michael Fill","doi":"10.1007/s00232-023-00301-0","DOIUrl":"10.1007/s00232-023-00301-0","url":null,"abstract":"<p><p>Concerted robust opening of cardiac ryanodine receptors' (RyR2) Ca<sup>2+</sup> release 1oplasmic reticulum (SR) is fundamental for normal systolic cardiac function. During diastole, infrequent spontaneous RyR2 openings mediate the SR Ca<sup>2+</sup> leak that normally constrains SR Ca<sup>2+</sup> load. Abnormal large diastolic RyR2-mediated Ca<sup>2+</sup> leak events can cause delayed after depolarizations (DADs) and arrhythmias. The RyR2-associated mechanisms underlying these processes are being extensively studied at multiple levels utilizing various model animals. Since there are well-described species-specific differences in cardiac intracellular Ca<sup>2+</sup> handing in situ, we tested whether or not single RyR2 function in vitro retains this species specificity. We isolated RyR2-rich heavy SR microsomes from mouse, rat, rabbit, and human ventricular muscle and quantified RyR2 function using identical solutions and methods. The single RyR2 cytosolic Ca<sup>2+</sup> sensitivity was similar across these species. However, there were significant species differences in single RyR2 mean open times in both systole and diastole-like solutions. In diastole-like solutions, single rat/mouse RyR2 open probability and frequency of long openings (> 6 ms) were similar, but these values were significantly greater than those of either single rabbit or human RyR2s. We propose these in vitro single RyR2 functional differences across species stem from the species-specific RyR2 regulatory environment present in the source tissue. Our results show the single rabbit RyR2 functional attributes, particularly in diastole-like conditions, replicate those of single human RyR2 best among the species tested.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571957","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}
{"title":"Schisandrin B Alleviates LPS Induced Mitochondrial Damage in C28I2 Cells.","authors":"Fei Hu, WenJie Hu, Hongming Xu","doi":"10.1007/s00232-023-00299-5","DOIUrl":"10.1007/s00232-023-00299-5","url":null,"abstract":"<p><p>Osteoarthritis is a common joint disease characterized by damage to the joint cartilage that occurs throughout the entire joint tissue. This damage primarily manifests as pain in the affected area. In clinical practice, medication is commonly used to relieve pain, but the treatment's effectiveness is poor and recurrent attacks are likely. Schisandrin B is the most abundant biphenylcyclohexene lignan found in the traditional Chinese medicine Schisandra chinensis, and it possesses various pharmacological effects. This study aims to investigate the protective effect of Schisandrin B on mitochondrial damage in osteoarthritis (C28I2 cells) under an inflammatory environment induced by LPS. Cell proliferation and activity, scratch tests, and LDH release tests are utilized to assess cell growth and migration ability. The immunofluorescence assay was used to detect the expression levels of proliferation and apoptosis proteins. The Western Blot assay was used to detect the expression levels of mitochondrial fusion and division proteins. The JC-1 assay was used to detect changes in mitochondrial membrane potential. The mitochondrial fluorescence probe assay was used to detect mitochondrial activity. Through research, it was found that Schisandrin B promotes the proliferation, growth, and migration of C28I2 cells, reduces apoptosis of C28I2 cells, balances mitochondrial fusion and division, stabilizes mitochondrial membrane potential, and promotes mitochondrial activity in an LPS induced inflammatory environment.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571960","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}
Azadeh Fakhrioliaei, Sepideh Tanhaei, SeyedAbbas Pakmehr, Maha Noori Shakir, Maytham T Qasim, Maryam Hariri, Alireza Nouhi Kararoudi, Mohammad Valilo
{"title":"Potential Role of Nrf2, HER2, and ALDH in Cancer Stem Cells: A Narrative Review.","authors":"Azadeh Fakhrioliaei, Sepideh Tanhaei, SeyedAbbas Pakmehr, Maha Noori Shakir, Maytham T Qasim, Maryam Hariri, Alireza Nouhi Kararoudi, Mohammad Valilo","doi":"10.1007/s00232-024-00307-2","DOIUrl":"10.1007/s00232-024-00307-2","url":null,"abstract":"<p><p>Cancer is one of the main causes of death among humans, second only to cardiovascular diseases. In recent years, numerous studies have been conducted on the pathophysiology of cancer, and it has been established that this disease is developed by a group of stem cells known as cancer stem cells (CSCs). Thus, cancer is considered a stem cell disease; however, there is no comprehensive consensus about the characteristics of these cells. Several different signaling pathways including Notch, Hedgehog, transforming growth factor-β (TGF-β), and WNT/β-catenin pathways cause the self-renewal of CSCs. CSCs change their metabolic pathways in order to access easy energy. Therefore, one of the key objectives of researchers in cancer treatment is to destroy CSCs. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an essential role in the protection of CSCs from reactive oxygen species (ROS) and chemotherapeutic agents by regulating antioxidants and detoxification enzymes. Human epidermal growth factor receptor 2 (HER2) is a member of the tyrosine kinase receptor family, which contributes to the protection of cancer cells against treatment and implicated in the invasion, epithelial-mesenchymal transition (EMT), and tumorigenesis. Aldehyde dehydrogenases (ALDHs) are highly active in CSCs and protect the cells against damage caused by active aldehydes through the regulation of aldehyde metabolism. On the other hand, ALDHs promote the formation and maintenance of tumor cells and lead to drug resistance in tumors through the activation of various signaling pathways, such as the ALDH1A1/HIF-1α/VEGF axis and Wnt/β-catenin, as well as changing the intracellular pH value. Given the growing body of information in this field, in the present narrative review, we attempted to shed light on the function of Nrf2, HER2, and ALDH in CSCs.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736557","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}
{"title":"Quantal Properties of Voltage-Dependent Ca<sup>2+</sup> Release in Frog Skeletal Muscle Persist After Reduction of [Ca<sup>2+</sup>] in the Sarcoplasmic Reticulum.","authors":"J F Olivera, G Pizarro","doi":"10.1007/s00232-024-00309-0","DOIUrl":"10.1007/s00232-024-00309-0","url":null,"abstract":"<p><p>In skeletal muscle, the Ca<sup>2+</sup> release flux elicited by a voltage clamp pulse rises to an early peak that inactivates rapidly to a much lower steady level. Using a double pulse protocol the fast inactivation follows an arithmetic rule: if the conditioning depolarization is less than or equal to the test depolarization, then decay (peak minus steady level) in the conditioning release is approximately equal to suppression (unconditioned minus conditioned peak) of the test release. This is due to quantal activation by voltage, analogous to the quantal activation of IP3 receptor channels. Two mechanisms are possible. One is the existence of subsets of channels with different sensitivities to voltage. The other is that the clusters of Ca<sup>2+</sup>-gated Ryanodine Receptor (RyR) β in the parajunctional terminal cisternae might constitute the quantal units. These Ca<sup>2+</sup>-gated channels are activated by the release of Ca<sup>2+</sup> through the voltage-gated RyR α channels. If the RyR β were at the basis of quantal release, it should be modified by strong inhibition of the primary voltage-gated release. This was attained in two ways, by sarcoplasmic reticulum (SR) Ca<sup>2+</sup> depletion and by voltage-dependent inactivation. Both procedures reduced global Ca<sup>2+</sup> release flux, but SR Ca<sup>2+</sup> depletion reduced the single RyR current as well. The effect of both interventions on the quantal properties of Ca<sup>2+</sup> release in frog skeletal muscle fibers were studied under voltage clamp. The quantal properties of release were preserved regardless of the inhibitory maneuver applied. These findings put a limit on the role of the Ca<sup>2+</sup>-activated component of release in generating quantal activation.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068885","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}
{"title":"Streamlined Biotinylation, Enrichment and Analysis for Enhanced Plasma Membrane Protein Identification Using TurboID and TurboID-Start Biotin Ligases.","authors":"Mehmet Sarihan, Murat Kasap, Gurler Akpinar","doi":"10.1007/s00232-023-00303-y","DOIUrl":"10.1007/s00232-023-00303-y","url":null,"abstract":"<p><p>Plasma membrane proteins (PMPs) play pivotal roles in various cellular events and are crucial in disease pathogenesis, making their comprehensive characterization vital for biomedical research. However, the hydrophobic nature and low expression levels of PMPs pose challenges for conventional enrichment methods, hindering their identification and functional profiling. In this study, we presented a novel TurboID-based enrichment approach for PMPs that helped overcoming some of the existing limitations. We evaluated the efficacy of TurboID and its modified form, TurboID-START, in PMP enrichment, achieving efficient and targeted labelling of PMPs without the need for stable cell line generation. This approach resulted reduction in non-specific biotinylation events, leading to improved PMP enrichment and enabled assessment of the subcellular proteome associated with the plasma membrane. Our findings paved the way for studies targeting the dynamic nature of the plasma membrane proteome and aiming to capture transient associations of proteins with the plasma membrane. The novel TurboID-based enrichment approach presented here offers promising prospects for in-depth investigations into PMPs and their roles in cellular processes.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576926","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}