Wheatly MG (1999) J Exp Zool "Calcium homeostasis in crustacea: the evolving role of branchial, renal, digestive and hypodermal epithelia."

Wheatly MG

[J Exp Zool, 1999]

Crustaceans serve as an ideal model for the study of calcium homeostasis due to their natural molting cycle. Demineralization and remineralization of the calcified cuticle is accompanied by bidirectional Ca transfer across the primary Ca transporting epithelia: gills, antennal gland (kidney), digestive system, and cuticular hypodermis. The review will demonstrate how a continuum of crustaceans can be used as a paradigm for the evolution of Ca transport mechanisms. Generally speaking, aquatic crustaceans rely primarily on branchial Ca uptake and accordingly are affected by water Ca content; terrestrial crustaceans rely on intake of dietary Ca across the digestive epithelium. Synchrony of mineralization at the cuticle vs. storage sites will be presented Physiological and behavioral adaptations have evolved to optimize Ca balance during the molting cycle in different Ca environments. Intracellular Ca regulation reveals common mechanisms of apical and basolateral membrane transport as well as intracellular sequestration. Regulation of cell Ca concentration will be discussed in intermolt and during periods of the molting cycle when transepithelial Ca flux is significantly elevated. Molecular characterization of the sarco-/endoplasmic reticular Ca pump in aquatic species reveals the presence of two isoforms that originate from a single gene. This gene is differentially expressed during the molting cycle. Gene expression may be regulated by a suite of hormones including ecdysone, calcitonin, and vitamin D. Perspectives for future research are presented.

Burgoyne RD et al. (2015) Biochim Biophys Acta "Sense and specificity in neuronal calcium signalling."

Haynes LP, Burgoyne RD

[Biochim Biophys Acta, 2015]

Changes in the intracellular free calcium concentration ([Ca]i) in neurons regulate many and varied aspects of neuronal function over time scales from microseconds to days. The mystery is how a single signalling ion can lead to such diverse and specific changes in cell function. This is partly due to aspects of the Ca signal itself, including its magnitude, duration, localisation and persistent or oscillatory nature. The transduction of the Ca signal requires Cabinding to various Ca sensor proteins. The different properties of these sensors are important for differential signal processing and determine the physiological specificity of Ca(2+) signalling pathways. A major factor underlying the specific roles of particular Ca sensor proteins is the nature of their interaction with target proteins and how this mediates unique patterns of regulation. We review here recent progress from structural analyses and from functional analyses in model organisms that have begun to reveal the rules that underlie Ca sensor protein specificity for target interaction. We discuss three case studies exemplifying different aspects of Ca sensor/target interaction. This article is part of a special issue titled the 13th European Symposium on Calcium.

Kenyon CJ (1995) Cell "A perfect vulva every time: gradients and signaling cascades in C. elegans."

Kenyon CJ

[Cell, 1995]

For many years developmental biologists have been trying to learn whether patterning within fields of cells is driven by graded morphogens or by sequential signaling cascades...

Strange K et al. (2007) Cell Calcium "Physiological roles of STIM1 and Orai1 homologs and CRAC channels in the genetic model organism Caenorhabditis elegans."

Xing J, Yan X, Strange K, Lorin-Nebel C

[Cell Calcium, 2007]

The nematode Caenorhabditis elegans provides numerous experimental advantages for developing an integrative molecular understanding of physiological processes and has proven to be a valuable model for characterizing Ca(2+) signaling mechanisms. This review will focus on the role of Ca(2+) release activated Ca(2+) (CRAC) channel activity in function of the worm gonad and intestine. Inositol 1,4,5-trisphosphate (IP(3))-dependent oscillatory Ca(2+) signaling regulates contractile activity of the gonad and rhythmic posterior body wall muscle contraction (pBoc) required for ovulation and defecation, respectively. The C. elegans genome contains a single homolog of both STIM1 and Orai1, proteins required for CRAC channel function in mammalian and Drosophila cells. C. elegans STIM-1 and ORAI-1 are coexpressed in the worm gonad and intestine and give rise to robust CRAC channel activity when coexpressed in HEK293 cells. STIM-1 or ORAI-1 knockdown causes complete sterility demonstrating that the genes are essential components of gonad Ca(2+) signaling. Knockdown of either protein dramatically inhibits intestinal cell CRAC channel activity, but surprisingly has no effect on pBoc, intestinal Ca(2+) oscillations or intestinal ER Ca(2+) store homeostasis. CRAC channels thus do not play obligate roles in all IP(3)-dependent signaling processes in C. elegans. Instead, we suggest that CRAC channels carry out highly specialized and cell specific signaling roles and that they may function as a failsafe mechanism to prevent Ca(2+) store depletion under pathophysiological and stress conditions.

Ma Z et al. (2015) Pflugers Arch "Calcium homeostasis modulator (CALHM) ion channels."

Ma Z, Tanis JE, Foskett JK, Taruno A

[Pflugers Arch, 2015]

Calcium homeostasis modulator 1 (CALHM1), formerly known as FAM26C, was recently identified as a physiologically important plasma membrane ion channel. CALHM1 and its Caenorhabditis elegans homolog, CLHM-1, are regulated by membrane voltage and extracellular Ca(2+) concentration ([Ca(2+)]o). In the presence of physiological [Ca(2+)]o (1.5mM), CALHM1 and CLHM-1 are closed at resting membrane potentials but can be opened by strong depolarizations. Reducing [Ca(2+)]o increases channel open probability, enabling channel activation at negative membrane potentials. Together, voltage and Ca(2+) o allosterically regulate CALHM channel gating. Through convergent evolution, CALHM has structural features that are reminiscent of connexins and pannexins/innexins/LRRC8 (volume-regulated anion channel (VRAC)) gene families, including four transmembrane helices with cytoplasmic amino and carboxyl termini. A CALHM1 channel is a hexamer of CALHM1 monomers with a functional pore diameter of 14A. CALHM channels discriminate poorly among cations and anions, with signaling molecules including Ca(2+) and ATP able to permeate through its pore. CALHM1 is expressed in the brain where it plays an important role in cortical neuron excitability induced by low [Ca(2+)]o and in type II taste bud cells in the tongue that sense sweet, bitter, and umami tastes where it functions as an essential ATP release channel to mediate nonsynaptic neurotransmitter release. CLHM-1 is expressed in C. elegans sensory neurons and body wall muscles, and its genetic deletion causes locomotion defects. Thus, CALHM is a voltage- and Ca(2+) o-gated ion channel, permeable to large cations and anions, that plays important roles in physiology.

Singaravelu G et al. (2013) Cell Calcium "Calcium signaling surrounding fertilization in the nematode Caenorhabditis elegans."

Singaravelu G, Singson A

[Cell Calcium, 2013]

Calcium plays a prominent role during fertilization in many animals. This review focuses on roles of Ca(2+) during the events around fertilization in the model organism, Caenorhabditis elegans. Specifically, the role of Ca(2+) in sperm, oocytes and the surrounding somatic tissues during fertilization will be discussed, with the focus on sperm activation, meiotic maturation of oocytes, ovulation, sperm-egg interaction and fertilization.

Johnstone LS et al. (2010) J Cell Mol Med "STIM proteins: integrators of signalling pathways in development, differentiation and disease."

Dziadek MA, Johnstone LS, Graham SJ

[J Cell Mol Med, 2010]

The stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum Ca(2+) sensors, serving to detect changes in receptor-mediated ER Ca(2+) store depletion and to relay this information to plasma membrane localized proteins, including the store-operated Ca(2+) channels of the ORAI family. The resulting Ca(2+) influx sustains the high cytosolic Ca(2+) levels required for activation of many intracellular signal transducers such as the NFAT family of transcription factors. Models of STIM protein deficiency in mice, Drosophila melanogaster and Caenorhabditis elegans, in addition to the phenotype of patients bearing mutations in STIM1 have provided great insight into the role of these proteins in cell physiology and pathology. It is now becoming clear that STIM1 and STIM2 are critical for the development and functioning of many cell types, including lymphocytes, skeletal and smooth muscle myoblasts, adipocytes and neurons, and can interact with a variety of signalling proteins and pathways in a cell- and tissue-type specific manner. This review focuses on the role of STIM proteins in development, differentiation and disease, in particular highlighting the functional differences between STIM1 and STIM2.

Alvarez J et al. (2020) Cells "The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models."

Fonteriz RI, Garcia-Casas P, Montero M, Alvarez-Illera P, Alvarez J

[Cells, 2020]

Ca²⁺ is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca²⁺ signaling is one of the key events in the development of neurodegenerative processes, an idea called the &quot;calcium hypothesis&quot; of neurodegeneration. <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) is a very good model for the study of aging and neurodegeneration. In fact, many of the signaling pathways involved in longevity were first discovered in this nematode, and many models of neurodegenerative diseases have also been developed therein, either through mutations in the worm genome or by expressing human proteins involved in neurodegeneration (-amyloid, -synuclein, polyglutamine, or others) in defined worm tissues. The worm is completely transparent throughout its whole life, which makes it possible to carry out Ca²⁺ dynamics studies in vivo at any time, by expressing Ca²⁺ fluorescent probes in defined worm tissues, and even in specific organelles such as mitochondria. This review will summarize the evidence obtained using this model organism to understand the role of Ca²⁺ signaling in aging and neurodegeneration.

Cohen SM et al. (2015) Biochem Biophys Res Commun "Evolutionary and functional perspectives on signaling from neuronal surface to nucleus."

Tsien RW, Ma H, Cohen SM, Li B

[Biochem Biophys Res Commun, 2015]

Reliance on Ca(2+) signaling has been well-preserved through the course of evolution. While the complexity of Ca(2+) signaling pathways has increased, activation of transcription factors including CREB by Ca(2+)/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca(2+) sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a CaMKII-CaM nuclear translocation. This intricatepathway depends on a specific role for multiple Ca(2+)/CaM-dependent kinases and phosphatases: /CaMKII phosphorylates CaMKII to trap CaM; CaN dephosphorylates CaMKII to dispatch it to the nucleus; and PP2A induces CaM release from CaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.

Redlarski G et al. (2015) Biomed Res Int "The influence of electromagnetic pollution on living organisms: historical trends and forecasting changes."

Gradolewski D, Krawczuk M, Tojza P, Koncicki A, Ambroziak D, Redlarski G, Lewczuk B, Jakubiuk K, Jaworski J, Skarbek L, Piechocki J, Zak A

[Biomed Res Int, 2015]

Current technologies have become a source of omnipresent electromagnetic pollution from generated electromagnetic fields and resulting electromagnetic radiation. In many cases this pollution is much stronger than any natural sources of electromagnetic fields or radiation. The harm caused by this pollution is still open to question since there is no clear and definitive evidence of its negative influence on humans. This is despite the fact that extremely low frequency electromagnetic fields were classified as potentially carcinogenic. For these reasons, in recent decades a significant growth can be observed in scientific research in order to understand the influence of electromagnetic radiation on living organisms. However, for this type of research the appropriate selection of relevant model organisms is of great importance. It should be noted here that the great majority of scientific research papers published in this field concerned various tests performed on mammals, practically neglecting lower organisms. In that context the objective of this paper is to systematise our knowledge in this area, in which the influence of electromagnetic radiation on lower organisms was investigated, including bacteria, E. coli and B. subtilis, nematode, Caenorhabditis elegans, land snail, Helix pomatia, common fruit fly, Drosophila melanogaster, and clawed frog, Xenopus laevis.