The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae

Sal1p is a mitochondrial protein that belongs to the SCaMC (short calcium-binding mitochondrial carrier) subfamily of mitochondrial carriers. The presence of calcium-binding motifs facing the extramitochondrial space allows the regulation of the transport activity of these carriers by cytosolic calcium and provides a new mechanism to transduce calcium signals in mitochondria without the requirement of calcium entry in the organelle. We have studied its transport activity, finding that it is a carboxyatractyloside-resistant ATP-Mg carrier. Mitochondria from a disruption mutant of SAL1 have a 50% reduction in the uptake of ATP. We have also found a clear stimulation of ATP-transport activity by calcium, with an S0.5 of approx. 30 μM. Our results also suggest that Sal1p is a target of the glucose-induced calcium signal which is non-essential in wild-type cells, but becomes essential for transport of ATP into mitochondria in yeast lacking ADP/ATP translocases.

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Annexins and their role in the control of symbioses development of plants with nitrogen-fixing bacteria and arbuscular mycorrhizal fungi

Ecological genetics ◽

10.17816/ecogen18533 ◽

2020 ◽

Author(s):

Elena Anatolyevna Dolgikh ◽

Darya Vladimirovna Kustova

Keyword(s):

Mycorrhizal Fungi ◽

Calcium Binding ◽

Structural Organization ◽

Physiological Role ◽

Arbuscular Mycorrhizal ◽

Structural Similarity ◽

Binding Motifs ◽

Calcium Dependent ◽

Cellular Processes

Annexins belong to the superfamily of calcium-dependent phospholipid binding proteins. The participation of these proteins in the regulation of structural organization of membranes, vesicular transport and a variety of signal transduction pathways is important for many cellular processes. Despite the structural similarity with animal annexins, plant annexins are characterized by significant variability of the N-terminal region and modification of calcium-binding motifs in II and III repeats, while calcium-binding motifs in I and IV repetitions remain conservative. However, the physiological role of animal and plant annexins, as well as mechanisms of their influence on calcium metabolism, may be similar. This review focused on the latest data about the structure and functioning of plant annexins.

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DORN1/P2K1 and purino-calcium signalling in plants: making waves with extracellular ATP

Annals of Botany ◽

10.1093/aob/mcz135 ◽

2019 ◽

Vol 124 (7) ◽

pp. 1227-1242 ◽

Cited By ~ 8

Author(s):

Elsa Matthus ◽

Jian Sun ◽

Limin Wang ◽

Madhura G Bhat ◽

Amirah B Mohammad-Sidik ◽

...

Keyword(s):

Fluorescent Protein ◽

Calcium Signalling ◽

Cytosolic Calcium ◽

Extracellular Atp ◽

Calcium Wave ◽

Free Calcium ◽

Wild Type ◽

Root Responses ◽

Leaves And Roots ◽

Green Fluorescent

Abstract Background and Aims Extracellular ATP governs a range of plant functions, including cell viability, adaptation and cross-kingdom interactions. Key functions of extracellular ATP in leaves and roots may involve an increase in cytosolic free calcium as a second messenger (‘calcium signature’). The main aim here was to determine to what extent leaf and root calcium responses require the DORN1/P2K1 extracellular ATP receptor in Arabidopsis thaliana. The second aim was to test whether extracellular ATP can generate a calcium wave in the root. Methods Leaf and root responses to extracellular ATP were reviewed for their possible links to calcium signalling and DORN1/P2K1. Leaves and roots of wild type and dorn1 plants were tested for cytosolic calcium increase in response to ATP, using aequorin. The spatial abundance of DORN1/P2K1 in the root was estimated using green fluorescent protein. Wild type roots expressing GCaMP3 were used to determine the spatial variation of cytosolic calcium increase in response to extracellular ATP. Key Results Leaf and root ATP-induced calcium signatures differed markedly. The leaf signature was only partially dependent on DORN1/P2K1, while the root signature was fully dependent. The distribution of DORN1/P2K1 in the root supports a key role in the generation of the apical calcium signature. Root apical and sub-apical calcium signatures may operate independently of each other but an apical calcium increase can drive a sub-apical increase, consistent with a calcium wave. Conclusion DORN1 could underpin several calcium-related responses but it may not be the only receptor for extracellular ATP in Arabidopsis. The root has the capacity for a calcium wave, triggered by extracellular ATP at the apex.

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Sorcin is an early marker of neurodegeneration, Ca2+ dysregulation and endoplasmic reticulum stress associated to neurodegenerative diseases

Cell Death and Disease ◽

10.1038/s41419-020-03063-y ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Ilaria Genovese ◽

Flavia Giamogante ◽

Lucia Barazzuol ◽

Theo Battista ◽

Annarita Fiorillo ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Neurodegenerative Diseases ◽

Calcium Binding ◽

Cytosolic Calcium ◽

Sigma 1 Receptor ◽

Calcium Dependent ◽

Early Marker ◽

Sigma 1 ◽

Stress Dependent ◽

Er Calcium

Abstract Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), and targeting this process may be therapeutically beneficial. Under this perspective, it is important to study proteins that regulate calcium homeostasis in the cell. Sorcin is one of the most expressed calcium-binding proteins in the human brain; its overexpression increases endoplasmic reticulum (ER) calcium concentration and decreases ER stress in the heart and in other cellular types. Sorcin has been hypothesized to be involved in neurodegenerative diseases, since it may counteract the increased cytosolic calcium levels associated with neurodegeneration. In the present work, we show that Sorcin expression levels are strongly increased in cellular, animal, and human models of AD, PD, and HD, vs. normal cells. Sorcin partially colocalizes with RyRs in neurons and microglia cells; functional experiments with microsomes containing high amounts of RyR2 and RyR3, respectively, show that Sorcin is able to regulate these ER calcium channels. The molecular basis of the interaction of Sorcin with RyR2 and RyR3 is demonstrated by SPR. Sorcin also interacts with other ER proteins as SERCA2 and Sigma-1 receptor in a calcium-dependent fashion. We also show that Sorcin regulates ER calcium transients: Sorcin increases the velocity of ER calcium uptake (increasing SERCA activity). The data presented here demonstrate that Sorcin may represent both a novel early marker of neurodegenerative diseases and a response to cellular stress dependent on neurodegeneration.

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Distinct roles of the C2A and the C2B domain of the vesicular Ca2+ sensor synaptotagmin 9 in endocrine β-cells

Biochemical Journal ◽

10.1042/bj20061182 ◽

2007 ◽

Vol 403 (3) ◽

pp. 483-492 ◽

Cited By ~ 13

Author(s):

Florence Grise ◽

Nada Taib ◽

Carole Monterrat ◽

Valérie Lagrée ◽

Jochen Lang

Keyword(s):

Calcium Binding ◽

Cytosolic Calcium ◽

Calcium Sensor ◽

Β Cells ◽

Calcium Dependent ◽

Protein Receptor ◽

Large Dense Core Vesicles ◽

Endocrine Secretion ◽

Sensor Proteins ◽

High Degree

Synaptotagmins form a family of calcium-sensor proteins implicated in exocytosis, and these vesicular transmembrane proteins are endowed with two cytosolic calcium-binding C2 domains, C2A and C2B. Whereas the isoforms syt1 and syt2 have been studied in detail, less is known about syt9, the calcium sensor involved in endocrine secretion such as insulin release from large dense core vesicles in pancreatic β-cells. Using cell-based assays to closely mimic physiological conditions, we observed SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor)-independent translocation of syt9C2AB to the plasma membrane at calcium levels corresponding to endocrine exocytosis, followed by internalization to endosomes. The use of point mutants and truncations revealed that initial translocation required only the C2A domain, whereas the C2B domain ensured partial pre-binding of syt9C2AB to the membrane and post-stimulatory localization to endosomes. In contrast with the known properties of neuronal and neuroendocrine syt1 or syt2, the C2B domain of syt9 did not undergo calcium-dependent membrane binding despite a high degree of structural homology as observed through molecular modelling. The present study demonstrates distinct intracellular properties of syt9 with different roles for each C2 domain in endocrine cells.

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New Insights on KCa3.1 Channel Modulation

Current Pharmaceutical Design ◽

10.2174/1381612826666200316152645 ◽

2020 ◽

Vol 26 (18) ◽

pp. 2096-2101

Author(s):

Giuseppe Manfroni ◽

Francesco Ragonese ◽

Lorenzo Monarca ◽

Andrea Astolfi ◽

Loretta Mancinelli ◽

...

Keyword(s):

Potassium Channel ◽

Critical Role ◽

Calcium Signalling ◽

Typical Feature ◽

Open Probability ◽

Pharmacological Agents ◽

Channel Modulation ◽

Calcium Dependent ◽

Modelling Techniques ◽

Calcium Activated Potassium Channel

The human intermediate conductance calcium-activated potassium channel, KCa3.1, is involved in several pathophysiological conditions playing a critical role in cell secretory machinery and calcium signalling. The recent cryo-EM analysis provides new insights for understanding the modulation by both endogenous and pharmacological agents. A typical feature of this channel is the low open probability in saturating calcium concentrations and its modulation by potassium channel openers (KCOs), such as benzo imidazolone 1-EBIO, without changing calcium-dependent activation. In this paper, we proposed a model of KCOs action in the modulation of channel activity. The KCa3.1 channel has a very rich pharmacological profile with several classes of molecules that selectively interact with different binding sites of the channel. Among them, benzo imidazolones can be openers (positive modulators such as 1-EBIO, DC-EBIO) or blockers (negative modulators such as NS1619). Through computation modelling techniques, we identified the 1,4-benzothiazin-3-one as a promising scaffold to develop new KCa3.1 channel modulators. Further studies are needed to explore the potential use of 1-4 benzothiazine- 3-one in KCa3.1 modulation and its pharmacological application.

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Thyrotropin-releasing hormone rapidly and transiently stimulates cytosolic calcium-dependent protein phosphorylation in GH3 pituitary cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)34417-x ◽

1982 ◽

Vol 257 (13) ◽

pp. 7566-7573 ◽

Cited By ~ 15

Author(s):

D S Drust ◽

T F Martin

Keyword(s):

Protein Phosphorylation ◽

Cytosolic Calcium ◽

Thyrotropin Releasing Hormone ◽

Pituitary Cells ◽

Releasing Hormone ◽

Calcium Dependent ◽

Dependent Protein

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Genetic mapping and transcriptomic characterization of a new fuzzless-tufted cottonseed mutant

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkaa042 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qian-Hao Zhu ◽

Warwick Stiller ◽

Philippe Moncuquet ◽

Stuart Gordon ◽

Yuman Yuan ◽

...

Keyword(s):

Molecular Mechanisms ◽

Agronomic Traits ◽

Gene Families ◽

Mutant Phenotype ◽

Wild Type ◽

Calcium Dependent ◽

Dependent Protein ◽

Flanking Region ◽

Comparative Transcriptomic Analysis

Abstract Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.

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A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

Molecular Brain ◽

10.1186/s13041-020-00725-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Eder Gambeta ◽

Maria A. Gandini ◽

Ivana A. Souza ◽

Laurent Ferron ◽

Gerald W. Zamponi

Keyword(s):

Trigeminal Neuralgia ◽

Missense Mutation ◽

Neurotransmitter Release ◽

Trigeminal System ◽

Wild Type ◽

Calcium Dependent ◽

Whole Cell Patch Clamp ◽

C Terminus ◽

Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

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