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G Corfas

Publications and source records attributed to G Corfas.

14 recordsLinked to original sources
PubMed1995

Differential expression of ARIA isoforms in the rat brain.

ARIA, heregulin, neu differentiation factor, and glial growth factor are members of a new family of growth and differentiation factors whose effects have been assayed on Schwann cells, skeletal muscle cells, and mammary tumor cell lines. To gain insight into their roles in the CNS, we studied the expression of ARIA in the rat brain. We found ARIA mRNA in all cholinergic neurons throughout the CNS, including motor neurons and cells of the medial septal nucleus and the nucleus basalis of Meynert. We also found that ARIA induces tyrosine phosphorylation of a 185 kDa protein in central and peripheral targets of these cholinergic neurons. ARIA mRNA, however, is not restricted to cholinergic neurons, suggesting that it may also play a role at other types of synapses. Its distribution in germinal layers of the telencephalon and cerebellum suggests that it may also play a role in the proliferation and/or migration of neuronal and glial precursor cells.

Animals↗
PubMed1995

ARIA is concentrated in the synaptic basal lamina of the developing chick neuromuscular junction.

ARIA is a member of a family of polypeptide growth and differentiation factors that also includes glial growth factor (GGF), neu differentiation factor, and heregulin. ARIA mRNA is expressed in all cholinergic neurons of the central nervous systems of rats and chicks, including spinal cord motor neurons. In vitro, ARIA elevates the rate of acetylcholine receptor incorporation into the plasma membrane of primary cultures of chick myotubes. To study whether ARIA may regulate the synthesis of junctional synaptic acetylcholine receptors in chick embryos, we have developed riboprobes and polyclonal antibody reagents that recognize isoforms of ARIA that include an amino-terminal immunoglobulin C2 domain and examined the expression and distribution of ARIA in motor neurons and at the neuromuscular junction. We detected significant ARIA mRNA expression in motor neurons as early as embryonic day 5, around the time that motor axons are making initial synaptic contacts with their target muscle cells. In older embryos and postnatal animals, we found ARIA protein concentrated in the synaptic cleft at neuromuscular junctions, consistent with transport down motor axons and release at nerve terminals. At high resolution using immunoelectron microscopy, we detected ARIA immunoreactivity exclusively in the synaptic basal lamina in a pattern consistent with binding to synapse specific components on the presynaptic side of the basal lamina. These results support a role for ARIA as a trophic factor released by motor neuron terminals that may regulate the formation of mature neuromuscular synapses.

Amino Acid Sequence↗
PubMed1994

A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development.

ARIA acetylcholine receptor-inducing activity protein, is a member of a family of ligands that includes the Neu differentiation factor, heregulin, and glial growth factor. These ligands all act through one or more receptor tyrosine kinases of approximately 185 kDa. In some conditions these ligands promote proliferation, whereas in others they induce differentiation. ARIA was originally isolated from chick brain on the basis of its ability to induce synthesis of nicotinic acetylcholine receptors in skeletal muscle. In this paper we show that ARIA is expressed in the subventricular zone of the rat brain and that it enhances the development of oligodendrocytes from bipotential (O2A) glial progenitor cells. We have also found that ARIA induces tyrosine phosphorylation of a 185-kDa protein in O2A progenitor cells. ARIA does not increase bromodeoxyuridine incorporation by oligodendrocytes but is mitogenic when added to Schwann cells in vitro. Thus, ARIA accelerates the formation of oligodendrocytes in vitro and is expressed where it could exercise the same influence in vivo.

Animals↗
PubMed1993

ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family.

Motor neurons stimulate their postsynaptic muscle targets to synthesize neurotransmitter receptors. Polypeptide signaling molecules may mediate this inductive interaction. Here we report the purification of ARIA, a protein that stimulates the synthesis of muscle acetylcholine receptors, and the isolation of ARIA cDNA. Recombinant ARIA increases acetylcholine receptor synthesis greater than 3-fold, and it induces tyrosine phosphorylation of a 185 kd muscle protein. The ARIA cDNA hybridizes with mRNAs that are expressed in the spinal cord from E4, a time prior to the onset of neuromuscular synapse formation, through adulthood. By E7, hybridizing mRNAs are concentrated in motor neurons. Chicken ARIA is homologous to the rat Neu differentiation factor and human here-gulin, ligands for the receptor tyrosine kinase encoded by the neu (c-erbB2, HER2) proto-oncogene. Our data suggest that members of the ARIA protein family promote the formation and maintenance of chemical synapses and, furthermore, that receptor tyrosine kinases play important roles in this process.

Animals↗
PubMed1993

ARIA, a protein that stimulates acetylcholine receptor synthesis, also induces tyrosine phosphorylation of a 185-kDa muscle transmembrane protein.

Motoneurons promote the accumulation of acetylcholine receptors (AChRs) at developing neuromuscular synapses. The AChR-inducing activity protein ARIA, which is purified from chicken brain and increases the synthesis of AChRs in chicken myotubes, may play a crucial role in this process. Here we show that ARIA induces the rapid tyrosine phosphorylation of a M(r) 185,000 protein (p185) in muscle cells. Phosphorylation of p185 correlates with AChR induction at each stage of ARIA purification. Moreover, medium conditioned by spinal cord motoneurons stimulates AChR synthesis and p185 phosphorylation. Studies with membrane-impermeant reagents and 125I-labeled ARIA indicate that p185 is a transmembrane ARIA-receptor tyrosine kinase. Our data suggests that muscle AChR synthesis can be regulated through tyrosine phosphorylation.

Animals↗
PubMed1993

The number of Na+ channels in cultured chick muscle is increased by ARIA, an acetylcholine receptor-inducing activity.

ARIA is a glycoprotein purified from chick brain on the basis of its ACh receptor-inducing activity (ARIA). In this study we present evidence that ARIA increases the number of voltage-gated sodium channels in chick muscle as well as the number of ACh receptors (AChRs). Exposure of chick myotubes to ARIA increased by twofold the number of 3H-saxitoxin binding, an effect that is comparable to the increase of AChRs assayed by 125I-alpha-bungarotoxin (125I-alpha-BTX) binding. We also documented effects of ARIA on myoblasts: the number of 125I-alpha-BTX binding sites in the mononucleated muscle cells was increased by 1.5-fold, and the peak TTX-sensitive inward currents increased by the same amount. No change was detected in the voltage dependence of channel activation, in mean channel current, or in mean channel open time. Thus, the Na+ channel is the first molecule, other than AChR subunits, whose expression has been shown to be induced by ARIA. Since sodium channels are concentrated at motor end plates, our results provide circumstantial evidence that ARIA may regulate several genes expressed at developing neuromuscular junctions. Moreover, the finding that ARIA's effects extend to mononucleated myoblasts suggests that this protein may be important during the earliest stages of muscle formation and innervation.

Animals↗
PubMed1991

Morphology of a sensory neuron in Drosophila is abnormal in memory mutants and changes during aging.

Several mutations in Drosophila impair learning and the cAMP cascade. We report here that the fine morphology of an identified mechanosensory neuron is abnormal in two of these mutants, dunce (dnc) and rutabaga (rut). The neuron innervating the antero-notopleural bristle was filled with horseradish peroxidase and studied at the light- and electron-microscopy level. In the mutants dnc and rut, this neuron has an abnormally large number of side branches and varicosities in a defined segment of the axon. In wild-type flies, age tends to decrease the number of side branches and variacosities in the same axonal segment that is affected by the mutations. Ultrastructural studies are compatible with the interpretation that the varicosities are potential synaptic sites. The results suggest that the cAMP cascade plays a role in shaping neuronal connectivity.

Aging↗
PubMed1990

Pharmacological evidence for the involvement of the cAMP cascade in sensory fatigue in Drosophila.

We have investigated the effect of systemic treatment with drugs that affect the cAMP cascade on the sensory response and sensory fatigue in an identified mechanosensory neuron of Drosophila. Forskolin, an activator of adenylate cyclase, decreases the sensory response of the neuron. H7, an inhibitor of protein kinase, inhibits sensory fatigue. Octopaminergic ligands facilitate sensory fatigue. These results, together with our previous neurogenetic analysis of sensory fatigue in Drosophila (Corfas and Dudai 1990), corroborate the hypothesis that the cAMP cascade is involved in the generation and modulation of sensory fatigue.

Adenylyl Cyclases↗
PubMed1990

Adaptation and fatigue of a mechanosensory neuron in wild-type Drosophila and in memory mutants.

The mechanosensory neuron that innervates the anteronotopleural bristle of Drosophila melanogaster responds with a burst of action potentials to deflection of the bristle towards the body wall. The decay of the firing rate upon sustained deflection is typical of a slowly adapting mechanosensory neuron. Upon repeated monotonous stimulation, the response decreases and the kinetics of adaptation change; the response recovers after rest. This sensory fatigue depends on the duration of the stimuli and the rate of stimulation. Two mutants, rutabaga (rut) and dunce (dnc), which are defective in learning and in the activity of the cAMP cascade, show altered kinetics of sensory fatigue. In rut, which has a reduced cAMP synthesis, the mechanosensory neuron fatigues less rapidly, whereas in dnc, characterized by a reduced cAMP hydrolysis, the neuron fatigues more rapidly than in wild-type flies. The data suggest that the cAMP cascade plays a role in the mechanism of sensory fatigue. Our study shows, for the first time, the effect of memory mutations on functional properties of an identified neuron which subserves a modifiable behavior. The experimental system described here could also be useful for neurogenetic dissection of mechanosensory transduction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Habituation and dishabituation of a cleaning reflex in normal and mutant Drosophila.

Upon tactile stimulation of its thoracic bristle(s), Drosophila cleans with a patterned set of leg movements the field covered by the stimulated bristles. We demonstrate that this cleaning reflex undergoes habituation and dishabituation. Repeated monotonous stimulation of the bristles by controlled air puffs leads to decrement, and finally to disappearance, of leg response. Spontaneous recovery of the response takes place in a time-dependent manner. Restoration of response can also be obtained by application of a high-frequency stimulus directed to other bristles. A mutant, rut, which is defective in learning and in adenylate cyclase activity, can habituate and dishabituate, but habituation is abnormally short-lived. As opposed to both nonassociative and associative learning paradigms used in Drosophila to date, the cleaning reflex lends itself to some aspects of cellular analysis, since single sensory neurons that mediate the input and motor neurons that mediate the behavioral output are identifiable. The modified reflex should therefore be useful in establishing the effects of single gene mutations that affect behavioral plasticity on the development and properties of identified neurons that contribute to discrete modifiable behaviors.

Animals↗
PubMed1988

What is the possible contribution of Ca2+-stimulated adenylate cyclase to acquisition, consolidation and retention of an associative olfactory memory in Drosophila.

We have quantitatively analyzed the effect of the mutation rut, which lesions a Ca2+-stimulated subpopulation (or functional state) of adenylate cyclase, on acquisition, consolidation and retention of an olfactory associative memory in Drosophila. The classical conditioning paradigm developed by Tully and Quinn (1985) was employed. Our data indicate that rut reduces acquisition and short-term memory in this paradigm, yet does not abolish consolidation of residual memory into an anesthesia-resistant form. Assuming that the rut behavioral defect is not due to altered neuroanatomy, the data also suggest that the adenylate cyclase activity lesioned by rut is only one of the molecular processes required for acquisition and short-term memory. These different postulated processes seem to act in parallel but are probably recruited sequentially; the mechanism involving rut+ gene product is necessary for response prior to other mechanisms which do not require rut+. It is also suggested, on the basis of the present results combined with previous data, that processes which do not require Ca2+-activated cyclase can not fulfill the partial role of this enzyme during acquisition but can partially compensate for its absence in later phases of memory formation.

Adenylyl Cyclases↗