Calcium Sensor Receptor

Plants deploy cell-surface and intracellular receptors to detect pathogen attack and trigger innate immune responses. Inside host cells, families of nucleotide-binding/leucine-rich repeat (NLR) proteins serve as pathogen sensors or downstream mediators of immune defence outputs and cell death, which prevent disease. Established genetic underpinnings of NLR-mediated immunity revealed various strategies plants adopt to combat rapidly evolving microbial pathogens. The molecular mechanisms of NLR activation and signal transmission to components controlling immunity execution were less clear...

UNLABELLED: Sensory adaptation allows neurons to adjust their sensitivity and responses based on recent experience. The mechanisms that mediate continuous adaptation to stimulus history over seconds to hours long timescales, and whether these mechanisms can operate within a single sensory neuron type, are unclear. The single pair of AFD thermosensory neurons in C. elegans exhibits experience-dependent plasticity in their temperature response thresholds on both minutes- and hours-long timescales upon a temperature upshift...

Calcium ions (Ca2+ ) reduce NMDA receptor currents through several distinct mechanisms. Among these, calmodulin (CaM)-dependent inhibition (CDI) accomplishes rapid, reversible, and incomplete reduction of the NMDA receptor currents in response to elevations in intracellular Ca2+ . Quantitative and mechanistic descriptions of CDI of NMDA receptor-mediated signals have been marred by variability originating, in part, from differences in the conditions and metrics used to evaluate this process across laboratories...

Signaling by calcium ion (Ca2+ ) plays a prominent role in cell physiology, and these mechanisms are frequently altered in tumor cells. In this review, we consider the interplay of Ca2+ signaling and the functions of the proto-oncogene non-receptor tyrosine kinase c-Src in tumor cells, and the viral oncogenic variant v-Src in transformed cells. Also, other members of the Src-family kinases are considered in this context. The role of Ca2+ in the cell is frequently mediated by Ca2+ -binding proteins, where the Ca2+ -sensor protein calmodulin (CaM) plays a prominent, essential role in many cellular signaling pathways...

Earthworms are affected by physical stress, like injury, and by exposure to xenobiotics, such as the toxic metal cadmium (Cd), which enters the environment mainly through industry and agriculture. The stress response to the single and the combination of both stressors was examined in regenerative and unharmed tissue of Lumbricus terrestris to reveal if the stress response to a natural insult like injury (amputation) interferes with Cd detoxification mechanisms. We characterized the roles of metallothionein 1 (MT1) and MT2 isoforms, heat shock protein 70 as well as immune biomarkers such as the toll-like receptors (TLR) single cysteine cluster TLR and multiple cysteine cluster TLR...

Microglia are found pathologically at all stages of multiple sclerosis (MS) lesion development and are hypothesized to contribute to both inflammatory injury and neuroprotection in the MS brain. Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed, play an important role as environmental sensors, and are involved in calcium homeostasis for a variety of cells. TRPV4 modulates myeloid cell phagocytosis in the periphery and microglial motility in the central nervous system. We hypothesized that TRPV4 deletion would alter microglia phagocytosis in vitro and lessen disease activity and demyelination in experimental autoimmune encephalitis (EAE) and cuprizone-induced demyelination...

Agriculturally important crop plants emit a multitude of volatile organic compounds (VOCs), which are excellent indicators of their health status and their interactions with pathogens and pests. In this study, we have developed a novel cellular olfactory panel for detecting fungal pathogen-related VOCs we had identified in the field, as well as during controlled inoculations of several crop plants. The olfactory panel consists of seven stable HEK293 cell lines each expressing a functional Drosophila olfactory receptor as a biosensing element along with GCaMP6, a fluorescent calcium indicator protein...

Intracellular calcium signaling is involved in regulating the key functional mechanisms of the nervous system. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. A family of highly specialized neuronal proteins described in recent decades can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors...

Calcium (Ca2+ ) signaling consists of three steps: (1) initiation of a change in cellular Ca2+ concentration in response to a stimulus, (2) recognition of the change through direct binding of Ca2+ by its sensors, (3) transduction of the signal to elicit downstream responses. Recent studies have uncovered a central role for Ca2+ signaling in both layers of immune responses initiated by plasma membrane (PM) and intracellular receptors, respectively. These advances in our understanding are attributed to several lines of research, including invention of genetically-encoded Ca2+ reporters for the recording of intracellular Ca2+ signals, identification of Ca2+ channels and their gating mechanisms, and functional analysis of Ca2+ binding proteins (Ca2+ sensors)...

Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1, controls PI4KB activity through interaction with PI4KB and neuronal calcium sensor-1 or calneuron-1. Both APOLs are present in Golgi-derived autophagy-related protein 9A vesicles, which are involved in PI4KB trafficking...

In our hearing organ, sound is encoded at ribbon synapses formed by inner hair cells (IHCs) and spiral ganglion neurons (SGNs). How the underlying synaptic vesicle (SV) release is controlled by Ca2+ in IHCs of hearing animals remained to be investigated. Here, we performed patch-clamp SGN recordings of the initial rate of release evoked by brief IHC Ca2+ -influx in an ex vivo cochlear preparation from hearing mice. We aimed to closely mimic physiological conditions by perforated-patch recordings from IHCs kept at the physiological resting potential and at body temperature...

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which, depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble amyloid-beta oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+ -dependent expression of neuroprotective genes...

Phenols confer bioactivity to a plethora of organic compounds. Protecting the phenolic functionality with photoremovable protecting groups (PPGs) sensitive to two-photon excitation (2PE) can block the bioactivity and provide controlled release of these compounds in a spatially and temporally restricted manner by photoactivation with IR light. To develop an efficient 2PE-sensitive PPG for releasing phenols, the (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ) chromophore was functionalized at the C4 position with methyl, morpholine, methoxy, para-tolyl, and 3,4,5-trimethoxyphenyl groups to provide 4-methyl-CyHQ (Me-CyHQ), 4-morpholino-CyHQ (Mor-CyHQ), 4-methoxy-CyHQ (MeO-CyHQ), 4-( p -tolyl)-CyHQ ( p Tol-CyHQ), and 4-(3,4,5-trimethoxyphenyl)-CyHQ (TMP-CyHQ) PPGs...

The recruitment of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors underlies the strengthening of neuronal connectivity during learning and memory. This process is triggered by N-methyl-D-aspartate (NMDA) receptor-dependent postsynaptic Ca2+ influx. Synaptotagmin (Syt)-1 and -7 have been proposed as Ca2+ sensors for AMPA receptor exocytosis but are functionally redundant. Here, we identify a cytosolic C2 domain-containing Ca2+ -binding protein, Copine-6, that forms a complex with AMPA receptors...

Calmodulin (CaM) is a small, multifunctional calcium (Ca2+ )-binding sensor that binds and regulates the open probability of cardiac ryanodine receptor 2 (RyR2) at both low and high cytosolic Ca2+ concentrations. Recent isothermal titration calorimetry (ITC) studies of a number of peptides that correspond to different regions of human RyR2 showed that two regions of human RyR2 (3584-3602aa and 4255-4271aa) bind with high affinity to CaM, suggesting that these two regions might contribute to a putative RyR2 intra-subunit CaM-binding pocket...

The G protein-coupled estrogen receptor 1 (GPER1) has been proposed to mediate rapid responses to the steroid hormone estrogen. However, despite a strong interest in its potential role in cancer, whether it is indeed activated by estrogen and how this works remain controversial. To provide new tools to address these questions, we set out to determine the interactome of exogenously expressed GPER1. The combination of two orthogonal methods, namely APEX2-mediated proximity labeling and immunoprecipitation followed by mass spectrometry, gave us high-confidence results for 73 novel potential GPER1 interactors...

The development of efficient tools for predicting drug-induced cardiotoxicity in the preclinical phase would greatly benefit the drug development process. This study presents an SU-8 cantilever integrated with a single-crystal silicon strain sensor to enhance force sensitivity in toxicity screening methods based on changes in the contraction force of cardiomyocytes. The proposed cantilever device enables real-time measurements of cardiomyocytes contraction force with high sensitivity, thereby facilitating the assessment of drug cardiotoxicity...

The transient receptor potential (TRP) channel superfamily is a group of non-selective cation channels functioning as cellular sensors for a wide range of physical, chemical and environmental stimuli. According to sequence homology, TRP channels are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin). They are widely expressed in different cell types and tissues and have essential roles in various physiological and pathological processes by regulating the concentration of ions (Ca2+ , Mg2+ , Na+ and K+ ) and influencing intracellular signaling pathways...

Intracellular calcium (Ca2+ ) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca2+ entry (SOCE) is also a receptor-regulated Ca2+ entry pathway that maintains Ca2+ homeostasis by sensing reduced Ca2+ levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP3 )...

In plants, reactive oxygen species (ROS) have emerged as a multifunctional signaling molecules that modulate diverse stress and growth responses. Earlier studies on ROS in plants primarily focused on its toxicity and ROS-scavenging processes, but recent findings are offering new insights on its role in signal perception and transduction. Further, the interaction of cell wall receptors, calcium channels, HATPase, protein kinases, and hormones with NADPH oxidases (respiratory burst oxidase homologues (RBOHs), provides concrete evidence that ROS regulates major signaling cascades in different cellular compartments related to stress and growth responses...