Sensory stimulation evokes intracellular calcium signals in astrocytes; however, the timing of these signals is disputed. Here, we used novel combinations of genetically encoded calcium indicators ...for concurrent two-photon imaging of cortical astrocytes and neurons in awake mice during whisker deflection. We identified calcium responses in both astrocyte processes and endfeet that rapidly followed neuronal events (∼120 ms after). These fast astrocyte responses were largely independent of IP3R2-mediated signaling and known neuromodulator activity (acetylcholine, serotonin, and norepinephrine), suggesting that they are evoked by local synaptic activity. The existence of such rapid signals implies that astrocytes are fast enough to play a role in synaptic modulation and neurovascular coupling.
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•A sub-population of astrocyte calcium signals has similar temporal dynamics to neurons•These fast signals occur in both endfeet and fine processes•These fast signals are largely independent of IP3R2 and neuromodulatory pathways
Stobart et al. have identified fast astrocyte calcium signals that rapidly follow neuronal signals evoked by whisker stimulation in awake mice. These astrocyte signal dynamics are sufficiently fast to influence cortical information processing and/or neurovascular coupling.
Cytosolic calcium signaling is critical for regulating downstream responses in plants encountering unfavorable environmental conditions.
In a genetic screen for Arabidopsis thaliana mutants defective ...in stress-induced cytosolic free Ca2+ (Ca2+cyt) elevations, we identified the R2R3-MYB transcription factor MYB30 as a regulator of Ca2+cyt in response to H2O2 and heat stresses.
Plants lacking MYB30 protein exhibited greater elevation of Ca2+cyt in response to oxidative and heat stimuli. Real-time reverse transcription–polymerase chain reaction (RT-PCR) results indicated that the expression of a number of ANNEXIN (ANN) genes, which encode Ca2+-regulated membrane-binding proteins modulating cytosolic calcium signatures, were upregulated in myb30 mutants. Further analysis showed that MYB30 bound to the promoters of ANN1 and ANN4 and repressed their expression. myb30 mutants were sensitive to methyl viologen (MV) and heat stresses. The H2O2- and heat-induced abnormal Ca2+cyt in myb30 was dependent on the function of ANN proteins. Moreover, the MV and heat sensitivity of myb30 was suppressed in mutants lacking ANN function or by application of LaCl3, a calcium channel blocker.
These results indicate that MYB30 regulates oxidative and heat stress responses through calcium signaling, which is at least partially mediated by ANN1 and ANN4.
Rotavirus causes severe diarrheal disease in children by broadly dysregulating intestinal homeostasis. However, the underlying mechanism(s) of rotavirus-induced dysregulation remains unclear. We ...found that rotavirus-infected cells produce paracrine signals that manifested as intercellular calcium waves (ICWs), observed in cell lines and human intestinal enteroids. Rotavirus ICWs were caused by the release of extracellular adenosine 5'-diphosphate (ADP) that activated P2Y1 purinergic receptors on neighboring cells. ICWs were blocked by P2Y1 antagonists or CRISPR-Cas9 knockout of the P2Y1 receptor. Blocking the ADP signal reduced rotavirus replication, inhibited rotavirus-induced serotonin release and fluid secretion, and reduced diarrhea severity in neonatal mice. Thus, rotavirus exploited paracrine purinergic signaling to generate ICWs that amplified the dysregulation of host cells and altered gastrointestinal physiology to cause diarrhea.
Low temperatures have adverse impacts on plant growth, developmental processes, crop productivity and food quality. It is becoming clear that Ca
signaling plays a crucial role in conferring cold ...tolerance in plants. However, the role of Ca
involved in cold stress response needs to be further elucidated. Recent studies have shown how the perception of cold signals regulate Ca
channels to induce Ca
transients. In addition, studies have shown how Ca
signaling and its cross-talk with nitric oxide (NO), reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling pathways ultimately lead to establishing cold tolerance in plants. Ca
signaling also plays a key role through Ca
/calmodulin-mediated
signal responsive 1 (AtSR1/CAMTA3) when temperatures drop rapidly. This review highlights the current status in Ca
signaling-mediated cold tolerance in plants.
Calcium (Ca
) signaling is critical for cell function and cell survival. Mitochondria play a major role in regulating the intracellular Ca
concentration (Ca
). Mitochondrial Ca
uptake is an ...important determinant of cell fate and governs respiration, mitophagy/autophagy, and the mitochondrial pathway of apoptosis. Mitochondrial Ca
uptake occurs via the mitochondrial Ca
uniporter (MCU) complex. This review summarizes the present knowledge on the function of MCU complex, regulation of MCU channel, and the role of MCU in Ca
homeostasis and human disease pathogenesis. The channel core consists of four MCU subunits and essential MCU regulators (EMRE). Regulatory proteins that interact with them include mitochondrial Ca
uptake 1/2 (MICU1/2), MCU dominant-negative β-subunit (MCUb), MCU regulator 1 (MCUR1), and solute carrier 25A23 (SLC25A23). In addition to these proteins, cardiolipin, a mitochondrial membrane-specific phospholipid, has been shown to interact with the channel core. The dynamic interplay between the core and regulatory proteins modulates MCU channel activity after sensing local changes in Ca
, reactive oxygen species, and other environmental factors. Here, we highlight the structural details of the human MCU heteromeric assemblies and their known roles in regulating mitochondrial Ca
homeostasis. MCU dysfunction has been shown to alter mitochondrial Ca
dynamics, in turn eliciting cell apoptosis. Changes in mitochondrial Ca
uptake have been implicated in pathological conditions affecting multiple organs, including the heart, skeletal muscle, and brain. However, our structural and functional knowledge of this vital protein complex remains incomplete, and understanding the precise role for MCU-mediated mitochondrial Ca
signaling in disease requires further research efforts.
The calcium signal is a powerful and multifaceted tool by which cells can achieve specific outcomes. Cellular machinery important in tumour progression is often driven or influenced by changes in ...calcium ions; in some cases this regulation occurs within spatially defined regions. Over the past decade there has been a deeper understanding of how calcium signalling is remodelled in some cancers and the consequences of calcium signalling on key events such as proliferation, invasion and sensitivity to cell death. Specific calcium signalling pathways have also now been identified as playing important roles in the establishment and maintenance of multidrug resistance and the tumour microenvironment.
Mechanosensory Signaling in Astrocytes Turovsky, Egor A; Braga, Alice; Yu, Yichao ...
The Journal of neuroscience,
12/2020, Volume:
40, Issue:
49
Journal Article
Peer reviewed
Open access
Mechanosensitivity is a well-known feature of astrocytes, however, its underlying mechanisms and functional significance remain unclear. There is evidence that astrocytes are acutely sensitive to ...decreases in cerebral perfusion pressure and may function as intracranial baroreceptors, tuned to monitor brain blood flow. This study investigated the mechanosensory signaling in brainstem astrocytes, as these cells reside alongside the cardiovascular control circuits and mediate increases in blood pressure and heart rate induced by falls in brain perfusion. It was found that mechanical stimulation-evoked Ca
responses in astrocytes of the rat brainstem were blocked by (1) antagonists of connexin channels, connexin 43 (Cx43) blocking peptide Gap26, or Cx43 gene knock-down; (2) antagonists of TRPV4 channels; (3) antagonist of P2Y
receptors for ATP; and (4) inhibitors of phospholipase C or IP3 receptors. Proximity ligation assay demonstrated interaction between TRPV4 and Cx43 channels in astrocytes. Dye loading experiments showed that mechanical stimulation increased open probability of carboxyfluorescein-permeable membrane channels. These data suggest that mechanosensory Ca
responses in astrocytes are mediated by interaction between TRPV4 and Cx43 channels, leading to Cx43-mediated release of ATP which propagates/amplifies Ca
signals via P2Y
receptors and Ca
recruitment from the intracellular stores. In astrocyte-specific Cx43 knock-out mice the magnitude of heart rate responses to acute increases in intracranial pressure was not affected by Cx43 deficiency. However, these animals displayed lower heart rates at different levels of cerebral perfusion, supporting the hypothesis of connexin hemichannel-mediated release of signaling molecules by astrocytes having an excitatory action on the CNS sympathetic control circuits.
There is evidence suggesting that astrocytes may function as intracranial baroreceptors that play an important role in the control of systemic and cerebral circulation. To function as intracranial baroreceptors, astrocytes must possess a specialized membrane mechanism that makes them exquisitely sensitive to mechanical stimuli. This study shows that opening of connexin 43 (Cx43) hemichannels leading to the release of ATP is the key central event underlying mechanosensory Ca
responses in astrocytes. This astroglial mechanism plays an important role in the autonomic control of heart rate. These data add to the growing body of evidence suggesting that astrocytes function as versatile surveyors of the CNS metabolic milieu, tuned to detect conditions of potential metabolic threat, such as hypoxia, hypercapnia, and reduced perfusion.
Astrocytes tile the central nervous system, but their functions in neural microcircuits in vivo and their roles in mammalian behavior remain incompletely defined. We used two-photon laser scanning ...microscopy, electrophysiology, MINIscopes, RNA-seq, and a genetic approach to explore the effects of reduced striatal astrocyte Ca2+ signaling in vivo. In wild-type mice, reducing striatal astrocyte Ca2+-dependent signaling increased repetitive self-grooming behaviors by altering medium spiny neuron (MSN) activity. The mechanism involved astrocyte-mediated neuromodulation facilitated by ambient GABA and was corrected by blocking astrocyte GABA transporter 3 (GAT-3). Furthermore, in a mouse model of Huntington’s disease, dysregulation of GABA and astrocyte Ca2+ signaling accompanied excessive self-grooming, which was relieved by blocking GAT-3. Assessments with RNA-seq revealed astrocyte genes and pathways regulated by Ca2+ signaling in a cell-autonomous and non-cell-autonomous manner, including Rab11a, a regulator of GAT-3 functional expression. Thus, striatal astrocytes contribute to neuromodulation controlling mouse obsessive-compulsive-like behavior.
•Multiple approaches were used to assess striatal astrocyte Ca2+ signaling in vivo•Ambient GABA was altered when astrocyte signaling was reduced•Reduced astrocyte signaling resulted in excessive self-grooming in mice•Astrocytes contribute to neural circuits in vivo and OCD-like phenotypes in mice
The Khakh laboratory evaluated the consequences of genetically attenuating astrocyte calcium signaling in the adult mouse striatum in vivo. They discovered excessive self-grooming phenotypes, the mechanisms of which were explored at the molecular, cellular, and in vivo levels.
Abiotic stresses are the major limiting factors influencing the growth and productivity of plants species. To combat these stresses, plants can modify numerous physiological, biochemical, and ...molecular processes through cellular and subcellular signaling pathways. Calcium-dependent protein kinases (CDPKs or CPKs) are the unique and key calcium-binding proteins, which act as a sensor for the increase and decrease in the calcium (Ca) concentrations. These Ca flux signals are decrypted and interpreted into the phosphorylation events, which are crucial for signal transduction processes. Several functional and expression studies of different CPKs and their encoding genes validated their versatile role for abiotic stress tolerance in plants. CPKs are indispensable for modulating abiotic stress tolerance through activation and regulation of several genes, transcription factors, enzymes, and ion channels. CPKs have been involved in supporting plant adaptation under drought, salinity, and heat and cold stress environments. Diverse functions of plant CPKs have been reported against various abiotic stresses in numerous research studies. In this review, we have described the evaluated functions of plant CPKs against various abiotic stresses and their role in stress response signaling pathways.
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