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1.
Br J Pharmacol ; 149(5): 490-7, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17001303

RESUMEN

BACKGROUND AND PURPOSE: RANTES is an inflammatory chemokine with a critical role in T-lymphocyte activation and proliferation. Its effects are mediated through G protein-coupled heptahelical receptors (GPCRs). We show for the first time that RANTES activates the orphan G protein-coupled receptor 75 (GPR75). EXPERIMENTAL APPROACH: To identify a ligand for GPR75 we have used three different and independent methods, namely luciferase assay, bioluminescence assay and IP3 accumulation assay. KEY RESULTS: Treatment of cells expressing GPR75 with subnanomolar concentrations of RANTES led to stimulation of the luciferase activity in a reporter-gene assay, an increase in inositol trisphosphate, and intracellular Ca2+. The latter effect was blocked by the phospholipase-C inhibitor (PLC) U73122 indicating that Gq proteins mediate GPR75 signaling. RANTES enhanced the phosphorylation of AKT and mitogen-activated protein kinase (MAPK) in GPR75-transfected cells and this effect was blocked by the PLC inhibitor U73122 and the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. The hippocampal cell line HT22, which expresses GPR75 endogenously, but not the other known RANTES receptors, was used to study the effects of RANTES and GPR75 on neuronal survival. Treatment of HT22 cells with RANTES significantly reduced the neurotoxicity of amyloid-beta peptides, by activating PLC and PI3K. CONCLUSIONS AND IMPLICATIONS: This demonstrate clearly and undoubtedly the ability of RANTES to act on GPR75. Defects in the RANTES/GPR75-signaling pathway may contribute to neuroinflammatory and neurodegenerative processes as observed in Alzheimer's disease.


Asunto(s)
Calcio/metabolismo , Quimiocina CCL5/farmacología , Inosina Trifosfato/biosíntesis , Receptores Acoplados a Proteínas G/genética , Péptidos beta-Amiloides/farmacología , Androstadienos/farmacología , Animales , Células CHO , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Estrenos/farmacología , Femenino , Perfilación de la Expresión Génica , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Mediciones Luminiscentes/métodos , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirrolidinonas/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Transfección , Wortmanina
2.
Diabet Med ; 23(1): 90-3, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16409572

RESUMEN

AIMS: To evaluate an algorithm with glucose prediction capacity and continuous adaptation of patient parameters-a model predictive control (MPC) algorithm-to control blood glucose concentration during fasting conditions in patients with Type 1 diabetes. In the subcutaneous (sc) route within a closed loop system. METHODS: Paired experiments were performed in six patients. Over 8 h the MPC algorithm was used to control glucose with s.c. insulin administration and two different glucose monitoring protocols: first, the algorithm was provided with intravenous (i.v.) glucose values for insulin dosage calculation directly (i.v.-s.c. route). Then, in the second experiment, i.v. glucose values were fed to the MPC with a delay of 30 min to simulate s.c. glucose measurements ('s.c.'-s.c. route). In both experiments plasma glucose, insulin dosage, and serum insulin levels were analysed. RESULTS: Glucose concentration was brought from hyper- to normoglycaemia and kept in the physiological range (6-7 mmol/l) with both routes in all subjects. Mean glucose concentration reached the threshold of 7 mmol/l approximately 2 (i.v.-s.c. route) and 3 ('s.c.'-s.c. route) hours after the start of glucose control with the MPC. During the last 2 h of automated glucose control, mean glucose concentration was 6.3 +/- 0.2 mmol/l and 6.6 +/- 0.3 mmol/l for i.v.-s.c. and 's.c.'-s.c. route, respectively. Glucose concentration, insulin doses, and serum insulin levels did not differ significantly between routes (P > 0.05). CONCLUSIONS: The MPC algorithm is suitable for glucose control during fasting within an extracorporeal artificial beta-cell in the subcutaneous route Type 1 diabetic patients.


Asunto(s)
Algoritmos , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Administración Cutánea , Simulación por Computador , Esquema de Medicación , Ayuno , Femenino , Humanos , Insulina/administración & dosificación , Insulina/sangre , Sistemas de Infusión de Insulina , Masculino , Modelos Biológicos
3.
J Cell Sci ; 114(Pt 20): 3599-606, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11707512

RESUMEN

The neuropeptide head activator stimulates cell proliferation of neuronal precursor and neuroendocrine cells. The mitogenic signaling cascade requires Ca(2+) influx for which, as we show in this paper, the growth-factor-regulated Ca(2+)-permeable cation channel, GRC, is responsible. GRC is a member of the transient receptor potential channel family. In uninduced cells only low amounts of GRC are present on the plasma membrane but, upon stimulation with head activator, GRC translocates from an intracellular compartment to the cell surface. Head activator functions as an inducer of GRC translocation in neuronal and neuroendocrine cells, which express GRC endogenously, and also in COS-7 cells after transfection with GRC. Head activator is no direct ligand for GRC, but its action requires the presence of a receptor coupled to a pertussis-toxin inhibitable G-protein. Heterologously expressed GRC becomes activated by head activator, which results in opening of the channel and Ca(2+) influx. SK&F 96365, an inhibitor specific for TRP-like channels, blocks Ca(2+) entry and, consequently, translocation of GRC is prevented. Head activator-induced GRC activation and translocation are also inhibited by wortmannin and KN-93, blockers of the phosphatidylinositol 3-kinase and of the Ca(2+)/calmodulin-dependent kinase, respectively, which implies a role for both kinases in head-activator signaling to GRC.


Asunto(s)
Canales de Calcio/metabolismo , Calcio/metabolismo , Neuronas/efectos de los fármacos , Neuropéptidos/farmacología , Transducción de Señal , Androstadienos/farmacología , Animales , Bencilaminas/farmacología , Células CHO , Células COS , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/genética , Membrana Celular , Cricetinae , Inhibidores Enzimáticos/farmacología , Humanos , Imidazoles/farmacología , Microscopía Fluorescente , Modelos Biológicos , Neuronas/citología , Neuronas/fisiología , Técnicas de Placa-Clamp , Toxina del Pertussis , Transporte de Proteínas , Purinas/farmacología , Ácido Pirrolidona Carboxílico/análogos & derivados , Proteínas Recombinantes de Fusión/metabolismo , Roscovitina , Sulfonamidas/farmacología , Canales Catiónicos TRPV , Factores de Virulencia de Bordetella/farmacología , Wortmanina
4.
Hum Genet ; 108(6): 529-36, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11499680

RESUMEN

The two human proteins with a VPS10 domain, SorLA and sortilin, both bind neuropeptides. Searching for other VPS10-domain proteins in the database revealed three new putative human neuropeptide receptors. The new receptors were designated SorCS1, SorCS2 and SorCS3, due to their identical domain composition, which, except for the N-terminal VPS10 domain, differs from that of SorLA and sortilin. Using the databases of the human genome project we elucidated the exon-intron structures of the human VPS10-receptor genes. They contain many short exons, separated by introns, several of which extend over more than 50 kb. The three SorCS genes encompass more than 500 kb of genomic DNA and therefore represent some of the largest known human genes. All these genes map to chromosomal localisations of known genetic diseases, many of them neurological disorders, corresponding to the strong expression of these receptors in the brain. CpG islands are located in the first exon of each of the VPS10-receptor genes and might be involved in developmental or tissue-specific regulation of gene expression.


Asunto(s)
Exones/genética , Receptores de Neuropéptido/genética , Secuencia de Aminoácidos , Sitios de Unión , Northern Blotting , Mapeo Cromosómico , Islas de CpG/genética , ADN Complementario/química , ADN Complementario/genética , Evolución Molecular , Genes/genética , Datos de Secuencia Molecular , Filogenia , Isoformas de Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Distribución Tisular
5.
J Mol Biol ; 307(3): 799-813, 2001 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-11273702

RESUMEN

We have developed a comprehensive expressed sequence tag database search method and used it for the identification of new members of the G-protein coupled receptor superfamily. Our approach proved to be especially useful for the detection of expressed sequence tag sequences that do not encode conserved parts of a protein, making it an ideal tool for the identification of members of divergent protein families or of protein parts without conserved domain structures in the expressed sequence tag database. At least 14 of the expressed sequence tags found with this strategy are promising candidates for new putative G-protein coupled receptors. Here, we describe the sequence and expression analysis of five new members of this receptor superfamily, namely GPR84, GPR86, GPR87, GPR90 and GPR91. We also studied the genomic structure and chromosomal localization of the respective genes applying in silico methods. A cluster of six closely related G-protein coupled receptors was found on the human chromosome 3q24-3q25. It consists of four orphan receptors (GPR86, GPR87, GPR91, and H963), the purinergic receptor P2Y1, and the uridine 5'-diphosphoglucose receptor KIAA0001. It seems likely that these receptors evolved from a common ancestor and therefore might have related ligands. In conclusion, we describe a data mining procedure that proved to be useful for the identification and first characterization of new genes and is well applicable for other gene families.


Asunto(s)
Clonación Molecular/métodos , Etiquetas de Secuencia Expresada , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Cromosomas Humanos Par 3/genética , Secuencia Conservada , Bases de Datos como Asunto , Exones/genética , Perfilación de la Expresión Génica , Humanos , Intrones/genética , Ligandos , Ratones , Datos de Secuencia Molecular , Familia de Multigenes/genética , Filogenia , Mapeo Físico de Cromosoma , ARN Mensajero/análisis , ARN Mensajero/genética , Receptores de Superficie Celular/química , Receptores Acoplados a Proteínas G/química , Receptores Purinérgicos P2/química , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y1 , Alineación de Secuencia , Uridina Difosfato Glucosa/metabolismo
6.
Neuroreport ; 12(1): 29-32, 2001 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-11201086

RESUMEN

Here we describe the expression of a third member of the VPS10 domain containing receptor family, SorCS, during mouse embryonal and early postnatal nervous system development. SorCS is expressed in a unique transient and dynamic pattern in regions where cells proliferate, as well as in areas where already differentiated cells reside, including the cerebral cortex, the ventral tegmental area, and the globus pallidus. Transcripts were absent from fiber tracts hinting at a neuronal expression. The only exception was hybridization signals on the developing optic nerve correlating with the appearance of astrocytes migrating into the retina.


Asunto(s)
Ojo/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Mesencéfalo/metabolismo , Receptores de Superficie Celular/metabolismo , Telencéfalo/metabolismo , Animales , Dopamina/metabolismo , Ojo/embriología , Ojo/crecimiento & desarrollo , Mesencéfalo/embriología , Mesencéfalo/crecimiento & desarrollo , Ratones , Telencéfalo/embriología , Telencéfalo/crecimiento & desarrollo
7.
Mech Dev ; 100(2): 335-8, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11165493

RESUMEN

We report the identification of a fourth member of the VPS10 domain containing receptor family, SorCS2, highly expressed in the developing and mature murine central nervous system. During early central nervous system development its main site of expression is the floor plate. In addition, high transcript levels were detected transiently in a variety of brain regions including the dopaminergic midbrain nuclei and the dorsal thalamus. Outside the nervous system expression is detected in lung and heart and transiently in a variety of mesodermally derived tissues.


Asunto(s)
Proteínas Fúngicas/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/genética , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte Vesicular , Secuencia de Aminoácidos , Animales , Northern Blotting , Sistema Nervioso Central/embriología , Sistema Nervioso Central/metabolismo , Clonación Molecular , ADN Complementario/metabolismo , Corazón/embriología , Hibridación in Situ , Pulmón/embriología , Mesencéfalo/embriología , Ratones , Datos de Secuencia Molecular , Neuronas/metabolismo , Estructura Terciaria de Proteína , Distribución Tisular
8.
Brain Res Gene Expr Patterns ; 1(1): 13-6, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15018813

RESUMEN

The G-protein coupled receptors (GPCRs) characterized by seven transmembrane domains represent the largest receptor superfamily to date and are implied in diverse cell signaling events, its members being present in a diversity of organs and tissues. Here we report the expression of Gpr85, a novel member of this gene family during mouse embryonal development and in the adult brain. Transcripts of Gpr85 were detected predominantly in tissues of neuroectodermal origin. In the central nervous system Gpr85 was expressed during phases of early neuronal differentiation. Highest transcript levels were observed in the developing cerebral cortex, pointing to a specific function of this gene for differentiation processes in the cerebral cortex. In addition, expression was also detected in derivatives of the neural crest and developing teeth.

9.
J Cell Sci ; 113 Pt 24: 4475-85, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11082041

RESUMEN

The single transmembrane receptor SorLA is the mammalian orthologue of the head activator-binding protein, HAB, from hydra. The human neuronal precursor cell line NT2 and the neuroendocrine cell line BON produce head activator (HA) and respond to HA by entry into mitosis and cell proliferation. They express SorLA, and bind HA with nanomolar affinity. HA coupled to Sepharose is able to precipitate SorLA specifically proving that SorLA binds HA. Using antisera directed against extra- and intracellular epitopes we find SorLA as membrane receptor and as soluble protein released from cells into the culture medium. Cell lines differ strongly in processing of SorLA, with NT2 cells expressing SorLA mainly as membrane receptor, whereas release predominates in BON cells. Soluble SorLA lacks the intracellular domain and is shed from the transmembrane protein by a metalloprotease. Release from cells and brain slices is stimulated by HA and by phorbol ester, and it is blocked by a metalloprotease inhibitor and by lowering the temperature to 20 degrees C. Blockade of SorLA shedding and treatment of cells with SorLA antisense oligonucleotides lead to a decrease in the rate of cell proliferation. From this we conclude that SorLA is necessary to mediate the mitogenic effect of endogenous HA. HA enhances the translocation of SorLA from internal membranes to the cell surface and its internalization. In addition, HA stimulates SorLA synthesis hinting at an autocatalytic feedback loop in which the ligand activates production, processing, and translocation of its receptor.


Asunto(s)
Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso/metabolismo , Neuropéptidos/metabolismo , Receptores de LDL/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Línea Celular , Membrana Celular/metabolismo , Furina , Humanos , Proteínas Relacionadas con Receptor de LDL , Ligandos , Metaloendopeptidasas/metabolismo , Ratones , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Procesamiento Proteico-Postraduccional , Ácido Pirrolidona Carboxílico/análogos & derivados , Receptores de LDL/biosíntesis , Receptores de LDL/genética , Solubilidad , Subtilisinas/metabolismo
10.
Biochim Biophys Acta ; 1493(1-2): 269-72, 2000 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-10978537

RESUMEN

A new G-protein coupled receptor, GPR85, was identified in man and mouse, which is completely conserved at the amino acid level. Transcripts of gpr85 were found in several human brain regions and, at lower levels, in spleen and placenta, whereas in mouse, gpr85 is confined to the brain. The hgpr85 gene was localized to human chromosome 7q31 by the polymerase chain reaction utilizing a radiation hybrid panel.


Asunto(s)
Química Encefálica , Cromosomas Humanos Par 7 , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Mapeo Cromosómico , Etiquetas de Secuencia Expresada , Humanos , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Reacción en Cadena de la Polimerasa , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Alineación de Secuencia
11.
Biochim Biophys Acta ; 1491(1-3): 350-4, 2000 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-10760602

RESUMEN

We report the identification of a splice variant of SorCS, a member of the family of VPS10 domain containing receptors. These type I transmembrane proteins share the presence of internalization signals in their cytoplasmic tail as one common characteristic. We show that an alternatively spliced transcript of SorCS is generated by differential processing of a composite internal/terminal exon. This splice variant encodes a protein with an N-terminal VPS10 domain followed by a leucine-rich module and a transmembrane domain identical with the already described SorCS protein, but a divergent cytoplasmic tail. In contrast to the known intracellular regions of the related receptors, this splice variant contains no internalization or sorting signals.


Asunto(s)
Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/genética , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte Vesicular , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Encéfalo/metabolismo , Citoplasma/metabolismo , Proteínas Fúngicas/genética , Ratones , Datos de Secuencia Molecular , Isoformas de Proteínas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
Eur J Cell Biol ; 79(11): 810-5, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11139144

RESUMEN

CDC25 phosphatases play key roles in cell proliferation by activating cell cycle-specific cyclin-dependent kinases (CDKs). We identified four new splice variants in the amino-terminal regulatory region of human cdc25C and one in cdc25A. All variants except one retain an intact catalytic domain. Alternative splicing results in loss of phosphorylation sites for kinases like CDK and the calcium/calmodulin-dependent kinase II (CaMKII), which influence CDC25 activity and compartmental localization. In NT2 teratocarcinoma cells, induced for nerve cell differentiation, the smaller sized variant of cdc25C was upregulated. At the protein level both phosphorylation state and isoform distribution differed between cell lines and cell cycle phases.


Asunto(s)
Empalme Alternativo/genética , Proteínas de Ciclo Celular/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Fosfatasas cdc25/genética , Secuencia de Aminoácidos , Secuencia de Bases , Western Blotting , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Humanos , Datos de Secuencia Molecular , Isoformas de Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Células Tumorales Cultivadas , Fosfatasas cdc25/química , Fosfatasas cdc25/metabolismo
13.
Biochem Biophys Res Commun ; 266(2): 347-51, 1999 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-10600506

RESUMEN

A novel receptor, SorCS, was isolated from murine brain. It shows homology to the mosaic receptor SorLA and the neurotensin receptor sortilin based on a common VPS10 domain which is the hallmark of this new receptor family. In the N-terminus of SorCS two putative cleavage sites for the convertase furin mark the beginning of the VPS10 domain, followed by a module of imperfect leucine-rich repeats and a transmembrane domain. The short intracellular C-terminus contains consensus signals for rapid internalization. The identified putative binding motifs for SH2 and SH3 domains are unique in the family of VPS10 domain receptors. SorCS is predominantly expressed in brain, but also in heart, liver, and kidney. SorCS transcripts detected by in situ hybridization in the murine central nervous system point to a neuronal expression.


Asunto(s)
Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/genética , Receptores de LDL , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte Vesicular , Proteínas Adaptadoras del Transporte Vesicular , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Clonación Molecular , Proteínas Fúngicas/química , Hibridación in Situ , Glicoproteínas de Membrana/química , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/química , ARN Mensajero/metabolismo , Receptores de Superficie Celular/química , Alineación de Secuencia , Homología de Secuencia de Aminoácido
15.
Development ; 126(18): 4077-86, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10457016

RESUMEN

The neuropeptide head activator plays an important role for proliferation and determination of stem cells in hydra. By affinity chromatography a 200 kDa head-activator binding protein, HAB, was isolated from the multiheaded mutant of Chlorohydra viridissima. Partial amino acid sequences were used to clone the HAB cDNA which coded for a receptor with a unique alignment of extracellular modules, a transmembrane domain, and a short carboxy-terminal cytoplasmic tail. A mammalian HAB homologue with identical alignment of these modules is expressed early in brain development. Specific antibodies revealed the presence of HAB in hydra as a transmembrane receptor, but also as secreted protein, both capable of binding head activator. Secretion of HAB during regeneration and expression in regions of high determination potential hint at a role for HAB in regulating the concentration and range of action of head activator.


Asunto(s)
Hydra/fisiología , Neuropéptidos/metabolismo , Receptores de Péptidos/metabolismo , Secuencia de Aminoácidos , Animales , Clonación Molecular , Ectodermo , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica , Hydra/embriología , Hibridación in Situ , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Mutación , Ácido Pirrolidona Carboxílico/análogos & derivados , Regeneración , Homología de Secuencia de Aminoácido , Solubilidad
16.
Biochem Biophys Res Commun ; 254(1): 273-9, 1999 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-9920770

RESUMEN

Using a PCR-based cloning strategy we have isolated a cDNA from mouse brain and named it fex, because it codes for a novel putative G protein-coupled receptor expressed in follicles. The deduced amino acid sequence shows a higher degree of homology to the family of glycoprotein receptors, namely those for FSH, LH, and TSH, than to other G protein-coupled receptors. With 18 leucine-rich repeats FEX exhibits features in its N-terminal portion characterizing it as unique within the glycoprotein receptor family. In the adult mouse fex expression was detected in the male and female gonads, the adrenal medulla, and the olfactory bulb of the brain. During embryonic development fex transcripts were detected transiently in various tissues, particularly in selected regions of the central nervous system, the developing face, the intervertebral discs anlagen, and the limb buds. Because fex was expressed during periods of active morphogenesis, it may be an important receptor for signals controlling growth and differentiation of specific embryonic tissues.


Asunto(s)
Desarrollo Embrionario y Fetal , Regulación del Desarrollo de la Expresión Génica , Glicoproteínas/genética , Receptores de Superficie Celular/genética , Secuencia de Aminoácidos , Animales , Clonación Molecular , Femenino , Proteínas de Unión al GTP/metabolismo , Glicoproteínas/biosíntesis , Masculino , Ratones , Datos de Secuencia Molecular , Embarazo , Receptores de Superficie Celular/biosíntesis , Alineación de Secuencia
17.
Eur J Cell Biol ; 76(2): 119-24, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9696351

RESUMEN

The human neuroendocrine cell line BON was used to study second messengers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entry into mitosis. HA-induced mitosis is mediated by an inhibitory G protein, the action of which is blocked by pertussis toxin. HA signaling requires inhibition of the cAMP pathway, calcium influx, and hyperpolarization of cells. The latter is a very important and sensitive step involving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with specific inhibitors of this potassium channel. Pharmacology and RNA analysis suggest identity with the recently cloned Gardos-type potassium channel.


Asunto(s)
Calcio/metabolismo , Mitosis/efectos de los fármacos , Neuropéptidos/farmacología , Canales de Potasio Calcio-Activados , Canales de Potasio/fisiología , Comunicación Autocrina , Northern Blotting , Recuento de Células/efectos de los fármacos , Ciclo Celular , Clotrimazol/farmacología , AMP Cíclico/metabolismo , Citometría de Flujo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Sustancias de Crecimiento/fisiología , Humanos , Canales de Potasio de Conductancia Intermedia Activados por el Calcio , Neuropéptidos/agonistas , Neuropéptidos/metabolismo , Páncreas/citología , Potasio/metabolismo , Bloqueadores de los Canales de Potasio , Canales de Potasio/genética , Ácido Pirrolidona Carboxílico/análogos & derivados , Radioinmunoensayo , Sistemas de Mensajero Secundario/efectos de los fármacos , Transducción de Señal , Células Tumorales Cultivadas
18.
Mech Dev ; 70(1-2): 65-76, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9510025

RESUMEN

Recently, a new type of transmembrane protein with a unique combination of protein domains was characterized from human, rabbit and chicken. This protein exhibits features of the low-density lipoprotein receptor family and shows homology to the receptor of the neuropeptide head activator isolated from hydra. To study the temporal and spatial pattern of expression of this unusual new receptor we have isolated a murine homolog and, in accordance with its human counterpart, named it mSorLA. Northern blot analysis revealed the highest abundance of mSorLA transcripts in the adult brain, lower levels in a variety of other organs and expression during embryogenesis. In situ hybridization showed predominant localization in neurons of the cortex, the hippocampus and the cerebellum. During embryonic development mSorLA displayed a unique pattern of expression in the cerebral cortex, where a subpopulation of neurons was labeled before final differentiation. Transcripts of mSorLA were also detected outside the central nervous system in regions active in morphogenesis.


Asunto(s)
Corteza Cerebral/embriología , Corteza Cerebral/metabolismo , Receptores de LDL/genética , Animales , Corteza Cerebral/crecimiento & desarrollo , Pollos , Clonación Molecular , ADN Complementario/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Hibridación in Situ , Ratones , Mosaicismo , Conejos
19.
Cell Tissue Res ; 287(3): 507-12, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9023081

RESUMEN

Recently, a cDNA was isolated from hydra with extensive homology to a mammalian and invertebrate gene which codes for a protein called laminin binding protein (LBP). In this paper we describe the protein expression of the hydra LBP in Escherichia coli. On SDS gels the recombinant hydra LBP displayed an apparent molecular mass of 43 kDa, although the calculated mass, including six additional histidines, is 33.7 kDa. Polyclonal antibodies were produced against the hydra recombinant LBP. The antiserum reacted with a 42-kDa and a 43-kDa protein from Hydra vulgaris and from a multiheaded mutant of Chlorohydra viridissima, respectively. In hydra, LBP RNA and protein were highly expressed in cells with short cell cycles, such as all cells of the interstitial cell lineage, less in slowly cycling epithelial cells, and at very reduced levels or not at all in differentiated cells. Higher expression in the multiheaded mutant of C. viridissima than in H. vulgaris, the cells of which differ in doubling time, hint at a function in cell proliferation. This is supported by the finding that in vitro hydra LBP is a substrate for the cell-cycle-specific kinase CDC2.


Asunto(s)
ADN Complementario/química , Hydra/metabolismo , Laminina/metabolismo , Animales , Diferenciación Celular
20.
Differentiation ; 61(2): 95-101, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8983175

RESUMEN

A cDNA was isolated from Hydra vulgaris coding for a 360 amino acid long polypeptide with no significant similarity to any known protein. In situ hybridization showed that the corresponding transcript is expressed exclusively in endodermal cells of the hypostome, hence its name hyp 1. Hyp 1 therefore represents a highly specific marker for the head region of hydra. In accordance with this, we found that hyp 1 expression was strong in tissues regenerating a head. Hyp 1 reappeared early during head regeneration, namely 6-8 h after initiation of regeneration by cutting. These findings imply that hyp 1 is an excellent marker for monitoring early events in head-specific differentiation processes in hydra.


Asunto(s)
Biomarcadores , Marcadores Genéticos/genética , Cabeza/fisiología , Hydra/fisiología , Péptidos/genética , Proteínas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Diferenciación Celular/genética , Clonación Molecular , Cabeza/embriología , Hydra/embriología , Hibridación in Situ , Datos de Secuencia Molecular , Péptidos/metabolismo , Regeneración/genética , Distribución Tisular , Transcripción Genética
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