scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Cloning and characterization of an extracellular Ca 2+ -sensing receptor from bovine parathyroid

09 Dec 1993-Nature (Nature Publishing Group)-Vol. 366, Iss: 6455, pp 575-580
TL;DR: The cloning of complementary DNA encoding an extracellular Ca2+ -sensing receptor from bovine parathyroid is reported with pharmacological and functional properties nearly identical to those of the native receptor.
Abstract: Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.
Citations
More filters
Journal ArticleDOI
TL;DR: The findings suggest that the mGluRs provide a novel target for development of therepeutic agents that could have a significant impact on neuropharmacology.
Abstract: ▪ Abstract In the mid to late 1980s, studies were published that provided the first evidence for the existence of glutamate receptors that are not ligand-gated cation channels but are coupled to effector systems through GTP-binding proteins. Since those initial reports, tremendous progress has been made in characterizing these metabotropic glutamate receptors (mGluRs), including cloning and characterization of cDNA that encodes a family of eight mGluR subtypes, several of which have multiple splice variants. Also, tremendous progress has been made in developing new highly selective mGluR agonists and antagonists and toward determining the physiologic roles of the mGluRs in mammalian brain. These findings have exciting implications for drug development and suggest that the mGluRs provide a novel target for development of therepeutic agents that could have a significant impact on neuropharmacology.

3,091 citations


Cites background from "Cloning and characterization of an ..."

  • ...It has a surprisingly high homology (30% sequence identity) with mGluRs (24)....

    [...]

Journal ArticleDOI
TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.
Abstract: Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

2,998 citations

Journal ArticleDOI
TL;DR: Recently, glutamate has been shown to regulate ion channels and enzymes producing second messengers via specific receptors coupled to G-proteins, and the existence of these receptors is changing views on the functioning of fast excitatory synapses.

2,304 citations

Journal ArticleDOI
TL;DR: An overview of the physiologic, endocrinologic, and molecular biologic characteristics of vitamin D is provided and information on new selective analogs of 1alpha,25-dihydroyvitamin D3 for therapy is provided.

2,092 citations

PatentDOI
10 Aug 2001-Cell
TL;DR: A detailed analysis of the patterns of expression of T1Rs and T2Rs is presented, thus providing a view of the representation of sweet and bitter taste at the periphery.

1,652 citations


Cites background from "Cloning and characterization of an ..."

  • ...…the study of sweet taste perception should help us explore the hedonic aspects of tasteand mGluRs), are significantly more closely related across species ( 90% identity; Brown et al., 1993; Na- transduction, and perhaps understand why a spoonfulof-sugar helps the medicine go down.kanishi, 1992)....

    [...]

  • ...(b) Cladogram showing sequence similarity between human (h) and mouse (m) T1Rs and related receptors (Nakanishi, 1992; Brown et al., 1993; Herrada and Dulac, 1997; Matsunami and Buck, 1997; Ryba and Tirindelli, 1997; Kaupmann et al., 1997; Hoon et al., 1999); mouse V2Rs do not have human…...

    [...]

References
More filters
Journal ArticleDOI
TL;DR: A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described.
Abstract: A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described. The predictive accuracy is estimated to be around 75-80% for both prokaryotic and eukaryotic proteins.

4,517 citations

Journal ArticleDOI
23 Oct 1992-Science
TL;DR: The molecular and functional diversity of the glutamate receptors is reviewed and their implications for integrative brain function are discussed.
Abstract: The glutamate receptors mediate excitatory neurotransmission in the brain and are important in memory acquisition, learning, and some neurodegenerative disorders. This receptor family is classified in three groups: the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate, and metabotropic receptors. Recent molecular studies have shown that many receptor subtypes exist in all three groups of the receptors and exhibit heterogeneity in function and expression patterns. This article reviews the molecular and functional diversity of the glutamate receptors and discusses their implications for integrative brain function.

2,588 citations

Journal ArticleDOI
TL;DR: In higher eukaryotes, translation is modulated at the level of initiation by five aspects of mRNA structure: (i) the m7G cap; (ii) the primary sequence or context surrounding the AUG codon; (iii) the position of the Aug codon, i.e. whether or not it s “first”; (iv) secondary structure both upstream and downstream from the AUU; and (v) leader length.

1,908 citations

Journal ArticleDOI
03 Dec 1992-Nature
TL;DR: A complementary DNA encoding an electrogenic Na+ but not Cl−-dependent high-affinity glutamate transporter (named EAAC1) is isolated from rabbit small intestine by expression in Xenopus oocytes and transcripts are found in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart.
Abstract: Glutamate transport across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney proceeds by high- and low-affinity transport systems. High-affinity (Km 2-50 microM) transport systems have been described that are dependent on Na+ but not Cl- ions and have a preference for L-glutamate and D- and L-aspartate. In neurons high-affinity glutamate transporters are essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. We have isolated a complementary DNA encoding an electrogenic Na(+)- but not Cl(-)-dependent high-affinity glutamate transporter (named EAAC1) from rabbit small intestine by expression in Xenopus oocytes. We find EAAC1 transcripts in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart. The function and pharmacology of the expressed protein are characteristic of the high-affinity glutamate transporter already identified in neuronal tissues. The abnormal glutamate transport that is associated with certain neurodegenerative diseases and which occurs during ischaemia and anoxia could be due to abnormalities in the function of this protein.

1,346 citations

Journal ArticleDOI
TL;DR: Among the many calcium-binding proteins in the nervous system, parvalbumin, calbindin-D28K and calretinin are particularly striking in their abundance and in the specificity of their distribution.

1,272 citations