Cell-surface expression of a new splice variant of the mouse signal peptide peptidase.

The signal peptide peptidase (SPP) is an intramembrane-cleaving aspartyl protease that acts on type II transmembrane proteins. SPP substrates include signal peptides after they have been cleaved from a preprotein, hence the name. The known SPP isoform, which we renamed SPPalpha, contains an endoplasmic reticulum retention signal at the carboxy terminus.

The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37.

The neuropeptide head activator (HA) is a mitogen for mammalian cell lines of neuronal or neuroendocrine origin. HA signalling is mediated by a G-protein-coupled receptor (GPCR). Orphan GPCRs with homology to peptide receptors were screened for HA interaction.

Characterisation and differential expression of two very closely related G-protein-coupled receptors, GPR139 and GPR142, in mouse tissue and during mouse development.

By searching the human and mouse genomic databases we found two G-protein-coupled receptors, GPR139 and GPR142, with characteristic motifs of the rhodopsin family of receptors. The gene for GPR139 maps to chromosome 7F1 of mouse and 16p12.3 of human and that for GPR142 to 11E2 of mouse and 17q25.

The orphan G-protein-coupled receptor GPR19 is expressed predominantly in neuronal cells during mouse embryogenesis.

G-protein-coupled receptors (GPCRs) are characterized by seven transmembrane domains and constitute the largest and structurally best-conserved family of signaling molecules. They are present in a diversity of organs and tissues and are involved in virtually all physiological processes. Here we report the expression of GPR19, an orphan GPCR, during mouse embryonic development and in the adult brain.

Identification of a mouse orthologue of the G-protein-coupled receptor SALPR and its expression in adult mouse brain and during development.

The mouse orthologue of somatostatin and angiotensin-like peptide receptor (SALPR) was amplified from cDNA of the hippocampal cell line HT22. It coded for a protein of 472 amino acids showing 84% sequence identity with human SALPR and 43% with human G-protein-coupled receptor 100 (GPR100). A distinct pattern of expression in brain, spinal cord, and dorsal root ganglia during development and in the mature brain hint at important functions of SALPR for differentiation and maintenance of the nervous system.

Loss of apolipoprotein E receptor LR11 in Alzheimer disease.

Background: Genetic, epidemiologic, and biochemical evidence suggests that apolipoprotein E, low-density lipoprotein receptors, and lipid metabolism play important roles in sporadic Alzheimer disease (AD).

Objective: To identify novel candidate genes associated with sporadic AD.

Design: We performed an unbiased microarray screen for genes differentially expressed in lymphoblasts of patients with sporadic AD and prioritized 1 gene product for further characterization in AD brain.

Cloning and characterization of a novel G-protein-coupled receptor with homology to galanin receptors.

We report the identification, cloning, and localization of human and mouse orthologues of a new G-protein-coupled receptor with homology to galanin receptors, which we termed galanin-receptor like (GalRL). The genes of GalRL were localized to chromosome 5q32 in human and to 18B3 in mouse. Northern blot analysis revealed expression of GalRL in the central nervous system of human and mouse and in 7- and 15-day-old mouse embryos.

The three sorCS genes are differentially expressed and regulated by synaptic activity.

We have isolated the murine sorCS3 gene, a new member of the family of receptors containing a Vps10p-domain. Receptors of this family facilitate rapid endocytosis and are thought to be involved in intracellular sorting. SorCS3 and the highly homologous sorCS1 and sorCS2 genes were expressed in a combinatorial, mostly non-overlapping pattern in both the developing and mature central nervous system.

Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled receptor GPR6 from mouse and induces intracellular Ca2+ release by activating the sphingosine-kinase pathway.

We identified and cloned the mouse orthologue of human GPR6 as a new member of the lysophospholipid-receptor family. Sphingosine-1-phosphate (S1P) activated GPR6, transiently expressed in frog oocytes or in Chinese hamster ovary (CHO) cells, with high specificity and nanomolar affinity. The GPR6 gene was found to be located on chromosome 10B1 and a single exon coded for the entire open-reading frame.

Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor.

G-protein-coupled receptor 100 (GPR100) was discovered by searching the human genome database for novel G-protein-coupled peptide receptors. Full-length GPR100 was amplified from a cDNA library of the neuroendocrine cell line BON, which is derived from a human pancreas carcinoid. The open-reading frame, present on a single exon, coded for a protein of 374 amino acids with highest sequence identity (43%) to the human orphan somatostatin- and angiotensin-like peptide receptor.

Expression of the presenilin-like signal peptide peptidase (SPP) in mouse adult brain and during development.

Recently, a new member of the presenilin family was identified as an aspartyl protease that cleaves signal peptides within hydrophobic domains, and was, therefore, named signal peptide peptidase (SPP). We isolated cDNAs coding for mouse and human orthologues of SPP. The human gene spans 55 kilobases on chromosome 20q11.

Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development.

Lysophospholipids are bioactive molecules influencing numerous cellular processes such as proliferation, differentiation, and motility. As extracellular ligands, they interact with specific members of the G-protein-coupled receptor family. We show in this paper that the lysophospholipid sphingosylphosphorylcholine is a high-affinity ligand for the orphan G-protein-coupled receptor GPR12.

Characterization of the VPS10 domain of SorLA/LR11 as binding site for the neuropeptide HA.

The single transmembrane receptor sorLA/LR11 contains binding domains typical for the low-density lipoprotein receptors and a VPS10 domain which, in the related receptor sortilin, binds the neuropeptide neurotensin. SorLA is synthesized as a proreceptor which is processed to the mature form by a furin-like propeptidase. Endogenous sorLA and its hydra homologue HAB bind the neuropeptide head activator (HA).

Isolation of a putative peroxidase, a target for factors controlling foot-formation in the coelenterate hydra.

In hydra, differentiated ectodermal cells of the foot region contain a peroxidase activity that can be used as a marker for foot-specific differentiation processes. Because the expression of the gene coding for the peroxidase must be tightly regulated during foot-specific differentiation, characterization of the protein and cloning of the corresponding gene should provide valuable tools for getting deeper insights into the regulation of foot-specific differentiation. In this paper we characterize the foot-specific peroxidase by biochemical, histochemical, and molecular biological methods.

GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors.

Background: Based on sequence similarity, the superfamily of G protein-coupled receptors (GPRs) can be subdivided into several subfamilies, the members of which often share similar ligands. The sequence data provided by the human genome project allows us to identify new GPRs by in silico homology screening, and to predict their ligands.

Results: By searching the human genomic database with known nucleotide receptors we discovered the gene for GPR99, a new orphan GPR.

The head and the foot inhibitor from hydra are not dowex artefacts.

In a recent publication in this journal (Berking 1983) it was claimed (1) that the head inhibitor we isolated from hydra is a Dowex artefact, (2) that a separate foot inhibitor does not exist in hydra and (3) that the only inhibitor that has so far been isolated from hydra is one which inhibits head and foot regeneration equally well. These statements are incorrect and require a response. In the following, I would like to summarise our evidence that the inhibitors isolated from hydra, including Berking's inhibitor, have different specificities for head and foot regeneration.

Analysis of morphogenetic mutants of hydra : IV.Reg-16, a mutant deficient in head regeneration.

The mutantreg-16 is deficient in head regeneration and abnormal in size regulation. The gastric region becomes twice as long as that of normal animals before the first bud is produced. Both mutant characteristics are due to changes in head-specific morphogen concentrations.

Properties of the foot inhibitor from hydra.

A substance was isolated from crude extracts of hydra that inhibits foot regeneration. This substance, the foot inhibitor, has a molecular weight of ≦500 daltons. It is a hydrophilic molecule, slightly basic in character and it has no peptide bonds.

Morphogenetic substances in nerve-depletedhydra.

By a double colchicine treatment the nerve-cell population ofhydra was reduced to less than 1% of the normal complement. Such severely nerve-depletedhydra contained normal or higher than normal concentrations of head activator, head inhibitor, foot activator and foot inhibitor which in normal animals are produced by nerve cells. According to typical chromatographic properties all four morphogenetic substances were chemically identical to those found in normal animals.

Separation and specificity of action of four morphogens from hydra.

A procedure is presented by which four previously described morphogenetic substances can be purified from hydra: an activator and an inhibitor of head formation and an activator and an inhibitor of foot formation. We show that all four substances act specifically. At low concentrations, the head factors only influence head and not foot formation, and the foot factors only influence foot and not head formation.

Head regeneration inHydra is initiated release of head activator and inhibitor.

Hydra regenerating heads release at least two substances into the surrounding medium: one stimulates and one inhibits head formation. The inhibitor is released mainly during the first hour after cutting, the activator is released more slowly with a maximum in the second hour and with substantial release still during the following six hours. The release of both substances seems to be specific for head regeneration: it is not found in animals regenerating feet.