Luka Lapajne, Christopher N Rudzitis, Brenan Cullimore, Daniel Ryskamp, Monika Lakk, Sarah N Redmon, Oleg Yarishkin, David Krizaj
{"title":"TRPV4: Cell type-specific activation, regulation and function in the vertebrate eye.","authors":"Luka Lapajne, Christopher N Rudzitis, Brenan Cullimore, Daniel Ryskamp, Monika Lakk, Sarah N Redmon, Oleg Yarishkin, David Krizaj","doi":"10.1016/bs.ctm.2022.07.005","DOIUrl":"10.1016/bs.ctm.2022.07.005","url":null,"abstract":"<p><p>The architecture of the vertebrate eye is optimized for efficient delivery and transduction of photons and processing of signaling cascades downstream from phototransduction. The cornea, lens, retina, vasculature, ciliary body, ciliary muscle, iris and sclera have specialized functions in ocular protection, transparency, accommodation, fluid regulation, metabolism and inflammatory signaling, which are required to enable function of the retina-light sensitive tissue in the posterior eye that transmits visual signals to relay centers in the midbrain. This process can be profoundly impacted by non-visual stimuli such as mechanical (tension, compression, shear), thermal, nociceptive, immune and chemical stimuli, which target these eye regions to induce pain and precipitate vision loss in glaucoma, diabetic retinopathy, retinal dystrophies, retinal detachment, cataract, corneal dysfunction, ocular trauma and dry eye disease. TRPV4, a polymodal nonselective cation channel, integrate non-visual inputs with homeostatic and signaling functions of the eye. The TRPV4 gene is expressed in most if not all ocular tissues, which vary widely with respect to the mechanisms of TRPV4 channel activation, modulation, oligomerization, and participation in protein- and lipid interactions. Under- and overactivation of TRPV4 may affect intraocular pressure, maintenance of blood-retina barriers, lens accommodation, neuronal function and neuroinflammation. Because TRPV4 dysregulation precipitates many pathologies across the anterior and posterior eye, the channel could be targeted to mitigate vision loss.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"89 ","pages":"189-219"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879314/pdf/nihms-1864291.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991258","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":"TRPV4-dependent signaling mechanisms in systemic and pulmonary vasculature.","authors":"Zdravka Daneva, Maniselvan Kuppusamy","doi":"10.1016/bs.ctm.2022.07.003","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.07.003","url":null,"abstract":"<p><p>The delicate balance between constrictor and dilator mechanisms is a vital determinant of blood pressure and blood flow. The maintenance of this balance requires constant communication between different cell-types in the vascular wall. In this regard, the transient receptor potential vanilloid type 4 (TRPV4) ion channel, a Ca<sup>2+</sup>-permeable non-selective cation channel, has emerged as a crucial regulator of Ca<sup>2+</sup>-mediated changes in vascular reactivity. Recent studies suggest that TRPV4 channels regulate vasoconstriction and arterial pressure in the systemic and pulmonary vasculature. New emerging data support a dilatory role of endothelial TRPV4 channels, and both constrictor and dilator roles of smooth muscle TRPV4 channels. Moreover, TRPV4 channel activity has been implicated in physiological functions of vascular support cells, such as fibroblasts and pericytes, to assist the sustenance of vascular reactivity in response to changes in intravascular pressure or external stimulation. Importantly, a growing body of evidence connects abnormal TRPV4 channel activity to multiple vascular disorders. This chapter will review the current literature on the cell-type specific roles of vascular TRPV4 channels in regulating physiological function. Additionally, we summarize our understanding of the contribution of abnormal TRPV4 channel activity to various vascular disorders.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"1-41"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33494616","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":"Role of TRPV4 in skeletal function and its mutant-mediated skeletal disorders.","authors":"Rashmita Das, Chandan Goswami","doi":"10.1016/bs.ctm.2022.07.004","DOIUrl":"https://doi.org/10.1016/bs.ctm.2022.07.004","url":null,"abstract":"<p><p>TRPV4 is a non-selective cation channel that belongs to the TRP super family. This channel can be activated by physiological temperatures and mechanical stimuli. In addition, TRPV4 is modulated by several endogenous mediators including specific lipids, cholesterol and their metabolic products. TRPV4 gene is present in all vertebrates and is widely expressed in tissues originating from ectoderm, endoderm and mesoderm. Although TRPV4 knockout is not lethal, point mutations in TRPV4 cause severe clinical phenotypes with variable penetration in human population. These mutations are mostly \"gain-of-function\" in nature and primarily affect muscles, bones and peripheral neurons, endorsing TRPV4 as critical regulator of musculoskeletal systems. Here we critically analyze the involvement of TRPV4 in musculoskeletal system. Studies of TRPV4 mutations provide detailed information on musculoskeletal disorders at molecular, cellular and metabolic levels.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"221-246"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33494618","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}
Angelo Rosario Carotenuto, Nhung Nguyen, Kathleen Cao, Anna Gaffney, Alan J Waring, Ka Yee C Lee, David Owen, Massimiliano Fraldi, Luca Deseri, Luka Pocivavsek
{"title":"Multiscale geometry and mechanics of lipid monolayer collapse.","authors":"Angelo Rosario Carotenuto, Nhung Nguyen, Kathleen Cao, Anna Gaffney, Alan J Waring, Ka Yee C Lee, David Owen, Massimiliano Fraldi, Luca Deseri, Luka Pocivavsek","doi":"10.1016/bs.ctm.2021.08.003","DOIUrl":"https://doi.org/10.1016/bs.ctm.2021.08.003","url":null,"abstract":"<p><p>Langmuir monolayers at gas/liquid interfaces provide a rich framework to investigate the interplay between multiscale geometry and mechanics. Monolayer collapse is investigated at a topological and geometric level by building a scale space M from experimental imaging data. We present a general lipid monolayer collapse phase diagram, which shows that wrinkling, folding, crumpling, shear banding, and vesiculation are a continuous set of mechanical states that can be approached by either tuning monolayer composition or temperature. The origin of the different mechanical states can be understood by investigating the monolayer geometry at two scales: fluorescent vs atomic force microscopy imaging. We show that an interesting switch in continuity occurs in passing between the two scales, C<sub>AFM</sub>∈M<sub>AFM</sub>≠C<sub>FM</sub>∈M. Studying the difference between monolayers that fold vs shear band, we show that shear banding is correlated to the persistence of a multi-length scale microstructure within the monolayer at all surface pressures. A detailed analytical geometric formalism to describe this microstructure is developed using the theory of structured deformations. Lastly, we provide the first ever finite element simulation of lipid monolayer collapse utilizing a direct mapping from the experimental image space M into a simulation domain P. We show that elastic dissipation in the form of bielasticity is a necessary and sufficient condition to capture loss of in-plane stability and shear banding.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"1-45"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560067","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":"Therapeutic perspectives of extracellular vesicles and extracellular microRNAs in atherosclerosis.","authors":"Ya-Ju Chang, Kuei-Chun Wang","doi":"10.1016/bs.ctm.2021.08.005","DOIUrl":"https://doi.org/10.1016/bs.ctm.2021.08.005","url":null,"abstract":"<p><p>Extracellular signaling molecules, such as growth factors, cytokines, and hormones, regulate cell behaviors and fate through endocrine, paracrine, and autocrine actions and play essential roles in maintaining tissue homeostasis. MicroRNAs, an important class of posttranscriptional modulators, could stably present in extracellular space and body fluids and participate in intercellular communication in health and diseases. Indeed, recent studies demonstrated that microRNAs could be secreted through vesicular and non-vesicular routes, transported in body fluids, and then transmitted to recipient cells to regulate target gene expression and signaling events. Over the past decade, a great deal of effort has been made to investigate the functional roles of extracellular vesicles and extracellular microRNAs in pathological conditions. Emerging evidence suggests that altered levels of extracellular vesicles and extracellular microRNAs in body fluids, as part of the cellular responses to atherogenic factors, are associated with the development of atherosclerosis. This review article provides a brief overview of extracellular vesicles and perspectives of their applications as therapeutic tools for cardiovascular pathologies. In addition, we highlight the role of extracellular microRNAs in atherogenesis and offer a summary of circulating microRNAs in liquid biopsies associated with atherosclerosis.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"255-277"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560070","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}
Sandeep Kumar, Sanjoli Sur, Julian Perez, Catherine Demos, Dong-Won Kang, Chan Woo Kim, Sarah Hu, Ke Xu, Jing Yang, Hanjoong Jo
{"title":"Atorvastatin and blood flow regulate expression of distinctive sets of genes in mouse carotid artery endothelium.","authors":"Sandeep Kumar, Sanjoli Sur, Julian Perez, Catherine Demos, Dong-Won Kang, Chan Woo Kim, Sarah Hu, Ke Xu, Jing Yang, Hanjoong Jo","doi":"10.1016/bs.ctm.2021.08.004","DOIUrl":"https://doi.org/10.1016/bs.ctm.2021.08.004","url":null,"abstract":"<p><p>Hypercholesterolemia is a well-known pro-atherogenic risk factor and statin is the most effective anti-atherogenic drug that lowers blood cholesterol levels. However, despite systemic hypercholesterolemia, atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while the stable flow (s-flow) regions are spared. Given their predominant effects on endothelial function and atherosclerosis, we tested whether (1) statin and flow regulate the same or independent sets of genes and (2) statin can rescue d-flow-regulated genes in mouse artery endothelial cells in vivo. To test the hypotheses, C57BL/6 J mice (8-week-old male, n=5 per group) were pre-treated with atorvastatin (10mg/kg/day, Orally) or vehicle for 5 days. Thereafter, partial carotid ligation (PCL) surgery to induce d-flow in the left carotid artery (LCA) was performed, and statin or vehicle treatment was continued. The contralateral right carotid artery (RCA) remained exposed to s-flow to be used as the control. Two days or 2 weeks post-PCL surgery, endothelial-enriched RNAs from the LCAs and RCAs were collected and subjected to microarray gene expression analysis. Statin treatment in the s-flow condition (RCA+statin versus RCA+vehicle) altered the expression of 667 genes at 2-day and 187 genes at 2-week timepoint, respectively (P<0.05, fold change (FC)≥±1.5). Interestingly, statin treatment in the d-flow condition (LCA+statin versus LCA+vehicle) affected a limited number of genes: 113 and 75 differentially expressed genes at 2-day and 2-week timepoint, respectively (P<0.05, FC≥±1.5). In contrast, d-flow in the vehicle groups (LCA+vehicle versus RCA+vehicle) differentially regulated 4061 genes at 2-day and 3169 genes at 2-week timepoint, respectively (P<0.05, FC≥±1.5). Moreover, statin treatment did not reduce the number of flow-sensitive genes (LCA+statin versus RCA+statin) compared to the vehicle groups: 1825 genes at 2-day and 3788 genes at 2-week, respectively, were differentially regulated (P<0.05, FC≥±1.5). These results revealed that both statin and d-flow regulate expression of hundreds or thousands of arterial endothelial genes, respectively, in vivo. Further, statin and d-flow regulate independent sets of endothelial genes. Importantly, statin treatment did not reverse d-flow-regulated genes except for a small number of genes. These results suggest that both statin and flow play important independent roles in atherosclerosis development and highlight the need to consider their therapeutic implications for both.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"97-130"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39560073","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}
Jordan Fauser, Martin Brennan, Denis Tsygankov, Andrei V Karginov
{"title":"Methods for assessment of membrane protrusion dynamics.","authors":"Jordan Fauser, Martin Brennan, Denis Tsygankov, Andrei V Karginov","doi":"10.1016/bs.ctm.2021.09.005","DOIUrl":"https://doi.org/10.1016/bs.ctm.2021.09.005","url":null,"abstract":"<p><p>Membrane protrusions are a critical facet of cell function. Mediating fundamental processes such as cell migration, cell-cell interactions, phagocytosis, as well as assessment and remodeling of the cell environment. Different protrusion types and morphologies can promote different cellular functions and occur downstream of distinct signaling pathways. As such, techniques to quantify and understand the inner workings of protrusion dynamics are critical for a comprehensive understanding of cell biology. In this chapter, we describe approaches to analyze cellular protrusions and correlate physical changes in cell morphology with biochemical signaling processes. We address methods to quantify and characterize protrusion types and velocity, mathematical approaches to predictive models of cytoskeletal changes, and implementation of protein engineering and biosensor design to dissect cell signaling driving protrusive activity. Combining these approaches allows cell biologists to develop a comprehensive understanding of the dynamics of membrane protrusions.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"205-234"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39690563","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":"On, in, and under membrane.","authors":"Michael A Model, Irena Levitan","doi":"10.1016/S1063-5823(21)00040-5","DOIUrl":"https://doi.org/10.1016/S1063-5823(21)00040-5","url":null,"abstract":"","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"88 ","pages":"xi-xiv"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653638","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}
Susana Cavallero, Ana M Blázquez-Medela, Sandro Satta, Tzung K Hsiai
{"title":"Endothelial mechanotransduction in cardiovascular development and regeneration: emerging approaches and animal models.","authors":"Susana Cavallero, Ana M Blázquez-Medela, Sandro Satta, Tzung K Hsiai","doi":"10.1016/bs.ctm.2021.07.002","DOIUrl":"https://doi.org/10.1016/bs.ctm.2021.07.002","url":null,"abstract":"<p><p>Living cells are exposed to multiple mechanical stimuli from the extracellular matrix or from surrounding cells. Mechanoreceptors are molecules that display status changes in response to mechanical stimulation, transforming physical cues into biological responses to help the cells adapt to dynamic changes of the microenvironment. Mechanical stimuli are responsible for shaping the tridimensional development and patterning of the organs in early embryonic stages. The development of the heart is one of the first morphogenetic events that occur in embryos. As the circulation is established, the vascular system is exposed to constant shear stress, which is the force created by the movement of blood. Both spatial and temporal variations in shear stress differentially modulate critical steps in heart development, such as trabeculation and compaction of the ventricular wall and the formation of the heart valves. Zebrafish embryos are small, transparent, have a short developmental period and allow for real-time visualization of a variety of fluorescently labeled proteins to recapitulate developmental dynamics. In this review, we will highlight the application of zebrafish models as a genetically tractable model for investigating cardiovascular development and regeneration. We will introduce our approaches to manipulate mechanical forces during critical stages of zebrafish heart development and in a model of vascular regeneration, as well as advances in imaging technologies to capture these processes at high resolution. Finally, we will discuss the role of molecules of the Plexin family and Piezo cation channels as major mechanosensors recently implicated in cardiac morphogenesis.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":"87 ","pages":"131-151"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113082/pdf/nihms-1805370.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10706683","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}