Amino acids critical for lipid/s-interaction at the lipid-water-interface of TRPV5/TRPV6 remain different during vertebrate radiation: Relevance in cancer, bone disorders and other pathophysiologies.

TRPV5 and TRPV6 are members of the TRP superfamily of ion channels and are present in almost all vertebrates as linked-genes with high homology and functional similarities. Abnormalities in the regulation or function of these two channels cause multiple pathological conditions, making these highly relevant for several diseases and pharmacological applications. In this context, how these two channels differ from each other is largely unknown.

Conserved and Unique Mitochondrial Target Sequence of TRPV4 Can Independently Regulate Mitochondrial Functions.

Though mitochondria have their own genome and protein synthesis machineries, the majority of the mitochondrial proteins are actually encoded by the nuclear genome. Most of these mitochondrial proteins are imported into specific compartments of the mitochondria due to their mitochondrial target sequence (MTS). Unlike the nuclear target sequence, the MTS of most of the mitochondrial localized proteins remain poorly understood, mainly due to their variability, heterogeneity, unconventional modes of action, mitochondrial potential-dependent transport, and other complexities.

TRPV4 modulation affects mitochondrial parameters in adipocytes and its inhibition upregulates lipid accumulation.

Enhanced lipid-droplet formation by adipocytes is a complex process and relevant for obesity. Using knock-out animals, involvement of TRPV4, a thermosensitive ion channel in the obesity has been proposed. However, exact role/s of TRPV4 in adipogenesis and obesity remain unclear and contradictory.

Cytocompatible Hyperbranched Polyesters Capable of Altering the Ca Signaling in Neuronal Cells In Vitro.

Synthetic hyperbranched polyesters with potential therapeutic properties were synthesized using the bifunctional polyethylene glycol or PEG with different molecular weights, ca., 4000, 6000, and 20,000 g/mol, and the trifunctional -aconitic acid or TAA. During polycondensation, a fixed amount of PEG was allowed to react with varying amounts of TAA (1:1 and 1:3) to control the branching extents.

Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

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.

Orphan GPCR GPRC5C Facilitates Angiotensin II-Induced Smooth Muscle Contraction.

Background: GPCRs (G-protein-coupled receptors) play a central role in the regulation of smooth muscle cell (SMC) contractility, but the function of SMC-expressed orphan GPCR class C group 5 member C (GPRC5C) is unclear. The aim of this project is to define the role of GPRC5C in SMC in vitro and in vivo.

Methods: We studied the role of GPRC5C in the regulation of SMC contractility and differentiation in human and murine SMC in vitro, as well as in tamoxifen-inducible, SMC-specific GPRC5C knockout mice under basal conditions and in vascular disease in vivo.

TRPV4 Activator-Containing CMT-Hy Hydrogel Enhances Bone Tissue Regeneration by Enhancing Mitochondrial Health.

Treating different types of bone defects is difficult, complicated, time-consuming, and expensive. Here, we demonstrate that transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechanosensitive, thermogated, and nonselective cation channel, is endogenously present in the mesenchymal stem cells (MSCs). TRPV4 regulates both cytosolic Ca levels and mitochondrial health.

Modulation of calcium-influx by carboxymethyl tamarind‑gold nanoparticles promotes biomineralization for tissue regeneration.

Gold nanoparticles (AuNPs) have been reported to modulate bone tissue regeneration and are being extensively utilized in biomedical implementations attributable to their low cytotoxicity, biocompatibility and simplicity of functionalization. Lately, biologically synthesized nanoparticles have acquired popularity because of their environmentally acceptable alternatives for diverse applications. Here we report the green synthesis of AuNPs by taking the biopolymer Carboxymethyl Tamarind (CMT) as a unique reducing as well as a stabilizing agent.

Menthol causes mitochondrial Ca-influx, affects structure-function relationship and cools mitochondria.

Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is complex, and still poorly understood. In this work, we used a human osteosarcoma cell line (Saos-2) and analysed the effect of menthol, especially in terms of cellular, subcellular and molecular aspects.

Highly water-stable, luminescent, and monodisperse polymer-coated CsPbBr nanocrystals for imaging in living cells with better sensitivity.

Recently, CsPbX (X= Cl, Br, I) nanocrystals (NCs) have evolved as a potential contender for various optoelectronic applications due to some of their excellent photophysical properties. Their superior non-linear optical properties enable them to take part in bioimaging applications due to their longer penetration depth and less scattering effect in living cells. However, the poor stability of perovskite NCs in aqueous media still remains a great challenge for practical usage.

TRPV4 regulates mitochondrial Ca-status and physiology in primary murine T cells based on their immunological state.

T cell activation process is critically affected by temperature and intracellular Ca-signalling. Yet, the nature and the key molecules involved in such complex Ca-signalling is poorly understood. It is mostly assumed that ion channels present in the plasma membrane primarily regulate the cytosolic Ca-levels exclusively.

TRPV4 interacts with MFN2 and facilitates endoplasmic reticulum-mitochondrial contact points for Ca-buffering.

Aim: Mitochondrial fission-fusion events, distribution, and Ca-buffering abilities are relevant for several diseases, yet are poorly understood events. TRPV4 channels are a group of thermosensitive ion channel which regulate cellular and mitochondrial Ca-level. The underlying mechanisms of the change in mitochondrial dynamics upon modulation of TRPV4 channel are ill explored.

TRPV4 acts as a mitochondrial Ca-importer and regulates mitochondrial temperature and metabolism.

TRPV4 is associated with the development of neuropathic pain, sensory defects, muscular dystrophies, neurodegenerative disorders, Charcot Marie Tooth and skeletal dysplasia. In all these cases, mitochondrial abnormalities are prominent. Here, we demonstrate that TRPV4, localizes to a subpopulation of mitochondria in various cell lines.

Function and regulation of thermosensitive ion channel TRPV4 in the immune system.

Transient receptor potential vanilloid sub-type 4 (TRPV4) is a six transmembrane protein that acts as a non-selective Ca 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.