Current Topics in Membranes

Mitochondria actively contribute to cellular Ca2+ homeostasis. The molecular mechanisms of mitochondrial Ca2+ uptake and release are well characterized and are attributed to the multi-protein assembly of the mitochondrial Ca2+ uniporter complex (MCUC) and the mitochondrial sodium-calcium exchanger (NCLX), respectively. Hence, Ca2+ transfer from the endoplasmic reticulum (ER) and store-operated Ca2+ entry (SOCE) into the mitochondrial matrix has been quantitatively visualized on the subcellular level using targeted fluorescent biosensors...

Vascular smooth muscle cells express several isoforms of a number of classes of K+ channels. Potassium channels play critical roles in the regulation of vascular smooth muscle contraction as well as vascular smooth muscle cell proliferation or phenotypic modulation. There is ample evidence that it is Ca2+ that enables these two seemingly disparate functions to be tightly coupled both in healthy and disease processes. Because of the central position that potassium channels have in vasocontraction, vasorelaxation, membrane potential, and smooth muscle cell proliferation, these channels continue to possess the potential to serve as novel therapeutic targets in cardiovascular disease...

Cardiovascular disease is on the rise, partially due to the continued increase in metabolic syndrome. Advances in basic research on vascular ion transport have the potential to provide targets for therapeutic interventions. Vascular specificity, which includes different vascular beds having different characteristics and the macro- vs. microvasculature, is a vitally important variable in characterization of ion transport. At the cellular level, targeted fluorescent biosensors for Ca2+ , super-resolution microscopy, and organelle patch clamp electrophysiology enable more detailed studies...

No abstract text is available yet for this article.

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a urologic, chronic pelvic pain syndrome characterized by pelvic pain, pressure, or discomfort with urinary symptoms. Symptom exacerbation (flare) is common with multiple, perceived triggers including stress. Multiple transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) expressed in the bladder have specific tissue distributions in the lower urinary tract (LUT) and are implicated in bladder disorders including overactive bladder (OAB) and BPS/IC...

Kidneys are central for whole body water and electrolyte balance by first filtering plasma at the glomeruli and then processing the filtrate along the renal nephron until the final urine is produced. Renal nephron epithelial cells mediate transport of water and solutes which is under the control of systemic hormones as well as local mechanical stimuli arising from alterations in fluid flow. TRPV4 is a mechanosensitive Ca2+ channel abundantly expressed in different segments of the renal nephron. The accumulated evidence suggests a critical role for TRPV4 in sensing variations in flow rates...

Transient Receptor Potential Vanilloid 4 (TRPV4) is expressed in numerous cell types within the heart, yet the expression levels, subcellular localization, and functional relevance of TRPV4 in cardiac myocytes is under-appreciated. Recent data indicate a critical role of TRPV4 in both atrial and ventricular myocyte biology, with expression levels and channel function increasing following pathological scenarios including ischemia, myocardial infarction, mechanical stress, and inflammation. Excessive activation of TRPV4 at the cellular level contributes to enhanced Ca2+ entry which predisposes the cardiac myocyte to pro-arrhythmic Ca2+ overload and electrophysiological abnormalities...

The alveolo-capillary barrier is relatively impermeable, and facilitates gas exchange via the large alveolar surface in the lung. Disruption of alveolo-capillary barrier leads to accumulation of edema fluid in lung injury. Studies in animal models of various forms of lung injury provide evidence that TRPV4 channels play a critical role in disruption of the alveolo-capillary barrier and pathogenesis of lung injury. TRPV4 channels from capillary endothelial cells, alveolar epithelial cells, and immune cells have been implicated in the pathogenesis of lung injury...

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...

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...

Transient receptor potential vanilloid sub-type 4 (TRPV4) is a six transmembrane protein that acts as a non-selective Ca2+ channel. Notably, TRPV4 is present in almost all animals, from lower eukaryotes to humans and is expressed in diverse tissue and cell types. Accordingly, TRPV4 is endogenously expressed in several types of immune cells that represent both innate and adaptive immune systems of higher organism. TRPV4 is known to be activated by physiological temperature, suggesting that it acts as a molecular temperature sensor and thus plays a key role in temperature-dependent immune activation...

Transient receptor potential vanilloid 4 (TRPV4) channels are multi-modally activated cation permeable channels that are expressed most organ tissues including the skin. TRPV4 is highly expressed in the skin and functions in skin resident cells such as epidermal keratinocytes, melanocytes, immune mast cells and macrophages, and cutaneous neurons. TRPV4 plays many crucial roles in skin homeostasis to affect an extensive range of processes such as temperature sensation, osmo-sensation, hair growth, cell apoptosis, skin barrier integrity, differentiation, nociception and itch...

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 Ca2+ -permeable non-selective cation channel, has emerged as a crucial regulator of Ca2+ -mediated changes in vascular reactivity. Recent studies suggest that TRPV4 channels regulate vasoconstriction and arterial pressure in the systemic and pulmonary vasculature...

No abstract text is available yet for this article.

Cell division, aging, and stress recovery triggers spatial reorganization of cellular components in the cytoplasm, including membrane bound organelles, with molecular changes in their compositions and structures. However, it is not clear how these events are coordinated and how they integrate with regulation of molecular crowding. We use the budding yeast Saccharomyces cerevisiae as a model system to study these questions using recent progress in optical fluorescence microscopy and crowding sensing probe technology...

Liquid-liquid phase separation (LLPS) is a ubiquitous process that drives the formation of membrane-less intracellular compartments. This compartmentalization contains vastly different protein/RNA/macromolecule concentrations compared to the surrounding cytosol despite the absence of a lipid boundary. Because of this, LLPS is important for many cellular signaling processes and may play a role in their dysregulation. This chapter highlights recent advances in the understanding of intracellular phase transitions along with current methods used to identify LLPS in vitro and model LLPS in situ...

This review focuses on time-resolved neutron scattering, particularly time-resolved small angle neutron scattering (TR-SANS), as a powerful in situ noninvasive technique to investigate intra- and intermembrane transport and distribution of lipids and sterols in lipid membranes. In contrast to using molecular analogues with potentially large chemical tags that can significantly alter transport properties, small angle neutron scattering relies on the relative amounts of the two most abundant isotope forms of hydrogen: protium and deuterium to detect complex membrane architectures and transport processes unambiguously...

Mass spectrometry imaging (MSI) is a powerful tool for in situ mapping of analytes across a sample. With growing interest in lipid biochemistry, the ability to perform such mapping without antibodies has opened many opportunities for MSI and lipid analysis. Herein, we discuss the basics of MSI with particular emphasis on MALDI mass spectrometry and lipid analysis. A discussion of critical advancements as well as protocol details are provided to the reader. In addition, strategies for improving the detection of lipids, as well as applications in biomedical research, are presented...

Lipid membrane domains are supramolecular lateral heterogeneities of biological membranes. Of nanoscopic dimensions, they constitute specialized hubs used by the cell as transient signaling platforms for a great variety of biologically important mechanisms. Their property to form and dissolve in the bulk lipid bilayer endow them with the ability to engage in highly dynamic processes, and temporarily recruit subpopulations of membrane proteins in reduced nanometric compartments that can coalesce to form larger mesoscale assemblies...

Impact of different lipids on membrane structure/lipid order is critical for multiple biological processes. Laurdan microscopy provides a unique tool to assess this property in heterogeneous biological membranes. This review describes the general principles of the approach and its application in model membranes and cells. It also provides an in-depth discussion of the insights obtained using Laurdan microscopy to evaluate the differential effects of cholesterol, oxysterols and oxidized phospholipids on lipid packing of ordered and disordered domains in vascular endothelial cells...