Melanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia.

Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling.

Inter-membrane control of junctional InsP receptors by PIP.

Crosstalk between junctional membrane proteins is vital in the coordinated generation of cellular Ca signals. New evidence (Ivanova et al.) reveals the signaling lipid, phosphatidylinositol 4,5-bisphosphate (PIP) reaches across plasma membrane (PM)-endoplasmic reticulum (ER) junctions to regulate inositol 1,4,5-trisphosphate receptors, controlling the critical progression of local to global Ca signals mediating a spectrum of fundamental cellular responses.

Calcium Homeostasis Is Involved in the Modulation of Gene Expression by MSL2 in Imbalanced Genomes.

Aneuploidy is highly detrimental to organisms due to genomic imbalance. However, the influence of parental unbalanced genome conditions on gene expression of their offspring remains unclear, particularly in animals. To further explore the molecular regulatory mechanisms, we firstly analyzed the expression patterns of aneuploid offspring from different parents with unbalanced genomes via reciprocal crosses and studied the potential functions of male-specific lethal 2 (MSL2) in this process.

A bright cyan fluorescence calcium indicator for mitochondrial calcium with minimal interference from physiological pH fluctuations.

Genetically Encoded Calcium (Ca) indicators (GECIs) are indispensable tools for dissecting intracellular Ca signaling and monitoring cellular activities. Mitochondrion acts as a Ca sink and a central player for maintaining Ca homeostasis. Accurately monitoring Ca transients within the mitochondrial matrix that undergo constant pH fluctuations is challenging, as signals of most currently available GECIs suffer from artifacts induced by physiological pH variations.

STIM1 functions as a proton sensor to coordinate cytosolic pH with store-operated calcium entry.

The meticulous regulation of intracellular pH (pH) is crucial for maintaining cellular function and homeostasis, impacting physiological processes such as heart rhythm, cell migration, proliferation, and differentiation. Dysregulation of pH is implicated in various pathologies such as arrhythmias, cancer, and neurodegenerative diseases. Here, we explore the role of STIM1, an ER calcium (Ca) sensor mediating Store Operated Ca Entry (SOCE), in sensing pH changes.

Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer.

Background: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease.

Methods: The cagA and vacA genotypes of 87 H.

Quality improvement of threadfin bream (Nemipterus virgatus) surimi-gel using soy protein as a natural food additive.

Previously, we identified sarcoplasmic serine proteinase (SSP) as a modori-inducing proteinase from threadfin bream belly muscle. In this study, we investigated the autolytic activity of commercial threadfin bream surimi under modori-inducing conditions. High autolytic activity was detected in commercial surimi and was inhibited by a soybean trypsin inhibitor, indicating that SSP still remained in the commercial surimi.

Redox Enzymes P4HB and PDIA3 Interact with STIM1 to Fine-Tune Its Calcium Sensitivity and Activation.

Sensing the lowering of endoplasmic reticulum (ER) calcium (Ca), STIM1 mediates a ubiquitous Ca influx process called the store-operated Ca entry (SOCE). Dysregulated STIM1 function or abnormal SOCE is strongly associated with autoimmune disorders, atherosclerosis, and various forms of cancers. Therefore, uncovering the molecular intricacies of post-translational modifications, such as oxidation, on STIM1 function is of paramount importance.

The A-kinase anchoring protein Yotiao decrease the ER calcium content by inhibiting the store operated calcium entry.

The meticulous regulation of ER calcium (Ca) homeostasis is indispensable for the proper functioning of numerous cellular processes. Disrupted ER Ca balance is implicated in diverse diseases, underscoring the need for a systematic exploration of its regulatory factors in cells. Our recent genomic-scale screen identified a scaffolding protein A-kinase anchoring protein 9 (AKAP9) as a regulator of ER Ca levels, but the underlying molecular mechanisms remain elusive.

Effect of three unsaturated fatty acids on the protein oxidation and structure of myofibrillar proteins from rainbow trout (Oncorhynchus mykiss).

In this study, the impact of three unsaturated fatty acids (Oleic acid: OA, Eicosapentaenoic acid: EPA, Docosahexaenoic acid: DHA) on the oxidation and structure of rainbow trout myofibrillar protein (MP) was explored. The findings revealed a notable increase in carbonyl content (P < 0.05) and a significant decrease in total sulfhydryl content (P < 0.

Clinical experience sharing on gastric microneuroendocrine tumors: A case report.

Background: The majority of gastric neuroendocrine tumors (G-NENs) are present in various lesions under endoscopy, and they can be polypoid uplifts, submucosal tumors or papules, erosions, and ulcers. The lesions are mostly confined to the mucosal or submucosal layer, usually less than 2 cm, and exclusively localized to the gastric body or fundus. In type 1 G-NENs, about 22% of cases have no visible lesions under an endoscope, and such lesions can only be detected biopsies (microcarcinoids).

CGI1746 targets σR to modulate ferroptosis through mitochondria-associated membranes.

Ferroptosis is iron-dependent oxidative cell death. Labile iron and polyunsaturated fatty acid (PUFA)-containing lipids are two critical factors for ferroptosis execution. Many processes regulating iron homeostasis and lipid synthesis are critically involved in ferroptosis.

An apical Phe-His pair defines the Orai1-coupling site and its occlusion within STIM1.

Ca signal-generation through inter-membrane junctional coupling between endoplasmic reticulum (ER) STIM proteins and plasma membrane (PM) Orai channels, remains a vital but undefined mechanism. We identify two unusual overlapping Phe-His aromatic pairs within the STIM1 apical helix, one of which (F394-H398) mediates important control over Orai1-STIM1 coupling. In resting STIM1, this locus is deeply clamped within the folded STIM1-CC1 helices, likely near to the ER surface.

Molecular action mechanisms of two novel and selective calcium release-activated calcium channel antagonists.

The prototypical calcium release-activated calcium (CRAC) channel, composed of STIM1 and Orai1, is a sought-after drug target for treating autoimmune disorders. Herein, we identified two novel and selective CRAC channel inhibitors, the indole-like compound C63368 and pyrazole core-containing compound C79413, potently and reversibly inhibiting the CRAC channel with low micromolar ICs and sparing various off-target ion channels. These two compounds did not inhibit STIM1 activation or its coupling with Orai1, nor did they affect the channel's calcium-dependent fast inactivation.

Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.

The heart requires a variety of energy substrates to maintain proper contractile function. Glucose and long-chain fatty acids (FA) are the major cardiac metabolic substrates under physiological conditions. Upon stress, a shift of cardiac substrate preference toward either glucose or FA is associated with cardiac diseases.

Effects of Cold Plasma Pretreatment on the Synthesis of Polysaccharide from Pleurotus ostreatus.

Fungal polysaccharides have attracted wide attention because of their medical pharmaceutical and health care value. So far, many efforts have been made in strain improvement to produce polysaccharides on a large scale at low cost. Here, a novel cold plasma-induced strain improvement technology was employed to pretreat Pleurotus ostreatus CGMCC 5.

Cold plasma pretreatment reinforces the lignocellulose-derived aldehyde inhibitors tolerance and bioethanol fermentability for Zymomonas mobilis.

Background: Lignocellulose-derived aldehyde inhibitors seriously blocked the biorefinery of biofuels and biochemicals. To date, the economic production of lignocellulose-based products heavily relied on high productivities of fermenting strains. However, it was expensive and time-consuming for the achievable rational modification to strengthen stress tolerance robustness of aldehyde inhibitors.

Identifying 2PHDO as a SOCE inhibitor from Chinese herbal extracts.

STIM- and Orai-mediated store operated calcium entry (SOCE) is a ubiquitous Ca2+ signaling process, crucial for the proper function of immune, muscle and neuronal systems. To treat SOCE-related disorder or diseases of these systems, and to mechanistically dissect activation and function of SOCE, specific SOCE inhibitors are needed. However, strategies for developing new SOCE modifiers are still limited.

The roles and mechanism of STIM1 in tumorigenesis and metastasis.

STIM1 (stromal interaction molecule 1) is one of the key components of the store operated Ca entry channel (SOCE), which is located on the endoplasmic reticulum membrane and highly expressed in most kinds of tumors. STIM1 promotes tumorigenesis and metastasis by modulating the formation of invadopodia, promoting angiogenesis, mediating inflammatory response, altering the cytoskeleton and cell dynamics. However, the roles and mechanism of STIM1 in different tumors have not been fully elucidated.

Celastrol inhibits store operated calcium entry and suppresses psoriasis.

Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis. To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.