Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami
{"title":"Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.","authors":"Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami","doi":"10.1007/s00232-024-00319-y","DOIUrl":"10.1007/s00232-024-00319-y","url":null,"abstract":"<p><p>TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"345-364"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989402","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":"The Role of the Swollen State in Cell Proliferation.","authors":"Behor Eleazar Cohen","doi":"10.1007/s00232-024-00328-x","DOIUrl":"https://doi.org/10.1007/s00232-024-00328-x","url":null,"abstract":"<p><p>Cell swelling is known to be involved in various stages of the growth of plant cells and microorganisms but in mammalian cells how crucial a swollen state is for determining the fate of the cellular proliferation remains unclear. Recent evidence has increased our understanding of how the loss of the cell surface interactions with the extracellular matrix at early mitosis decreases the membrane tension triggering curvature changes in the plasma membrane and the activation of the sodium/hydrogen (Na +/H +) exchanger (NHE1) that drives osmotic swelling. Such a swollen state is temporary, but it is critical to alter essential membrane biophysical parameters that are required to activate Ca2 + channels and modulate the opening of K + channels involved in setting the membrane potential. A decreased membrane potential across the mitotic cell membrane enhances the clustering of Ras proteins involved in the Ca2 + and cytoskeleton-driven events that lead to cell rounding. Changes in the external mechanical and osmotic forces also have an impact on the lipid composition of the plasma membrane during mitosis.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559268","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}
Anwaar S Chaudary, Yanglin Guo, Yuri N Utkin, Maryam Barancheshmeh, Ruben K Dagda, Edward S Gasanoff
{"title":"Sphingomyelin Inhibits Hydrolytic Activity of Heterodimeric PLA<sub>2</sub> in Model Myelin Membranes: Pharmacological Relevance.","authors":"Anwaar S Chaudary, Yanglin Guo, Yuri N Utkin, Maryam Barancheshmeh, Ruben K Dagda, Edward S Gasanoff","doi":"10.1007/s00232-024-00327-y","DOIUrl":"https://doi.org/10.1007/s00232-024-00327-y","url":null,"abstract":"<p><p>In this work, the heterodimeric phospholipase A<sub>2</sub>, HDP-2, from viper venom was investigated for its hydrolytic activity in model myelin membranes as well as for its effects on intermembrane exchange of phospholipids (studied by phosphorescence quenching) and on phospholipid polymorphism (studied by <sup>1</sup>H-NMR spectroscopy) to understand the role of sphingomyelin (SM) in the demyelination of nerve fibers. By using well-validated in vitro approaches, we show that the presence of SM in model myelin membranes leads to a significant inhibition of the hydrolytic activity of HDP-2, decreased intermembrane phospholipid exchange, and reduced phospholipid polymorphism. Using AutoDock software, we show that the NH<sup>δ+</sup> group of the sphingosine backbone of SM binds to Tyr22(C=O<sub>pb</sub><sup>δ-</sup>) of HDP-2 via a hydrogen bond which keeps only the polar head of SM inside the HDP-2's active center and positions the sn-2 acyl ester bond away from the active center, thus making it unlikely to hydrolyze the alkyl chains at the sn-2 position. This observation strongly suggests that SM inhibits the catalytic activity of HDP-2 by blocking access to other phospholipids to the active center of the enzyme. Should this observation be verified in further studies, it would offer a tantalizing opportunity for developing effective pharmaceuticals to stop the demyelination of nerve fibers by aberrant PLA<sub>2</sub>s with overt activity - as observed in brain degenerative diseases - by inhibiting SM hydrolysis and/or facilitating SM synthesis in the myelin sheath membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512121","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}
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":"<p><p>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.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"165-205"},"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}
{"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":" ","pages":"151-164"},"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":" ","pages":"215-230"},"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":" ","pages":"245-256"},"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}
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":" ","pages":"25-36"},"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":" ","pages":"107-114"},"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}