A 42-kDa glycoprotein isolated from chicken brain, referred to as acetylcholine receptor-inducing activity (ARIA), that stimulates the rate of incorporation of acetyicholine receptors into the surface of chicken myotubes may play a role in the nerve-induced accumulation of receptors at developing neuromuscular synapses. Using nuclease-protection assays, we have found that ARIA causes a 2-to 16-fold increase in the level of mRNA encoding the a subunit of the receptor, with little or no change in the levels of y-and 8-subunit messengers. ARIA also increases the amount of a putative nuclear precursor of a-subunit mRNA, consistent with an activation of gene transcription. These results suggest that the concentration of a subunit may limit the rate of biosynthesis of the acetylcholine receptors in chicken myotubes. They also indicate that neuronal factors can regulate the expression of receptor subunit genes in a selective manner. Tetrodotoxin, 8-bromo-cAMP, and forskolin also increase the amount of a-subunit mRNA, with little change in the amount of v-and 6-subunit mRNAs. Unlike ARIA, however, these agents have little effect on the concentration of the a-subunit nuclear precursor.Motor neurons induce the accumulation of acetylcholine receptors (AcChoRs) at developing neuromuscularjunctions (reviewed in refs. 1-3). Two mechanisms have been found to contribute to this phenomenon. Motor neurons may promote the aggregation of receptors that were present on the myocyte surface before nerve-muscle contact, and they may increase the insertion of new receptors in the immediate vicinity of the synapse (4). Receptor aggregation is evident at chicken junctions, but, during the first 24 hr after contact, newly inserted receptors make up the great majority of those present (7). Several laboratories have characterized factors from neural tissue that alter the number or distribution of AcChoRs on cultured myotubes and that may, therefore, play a role in the accumulation of receptors at nascent synapses (8)(9)(10)(11)(12)(13)(14). Little is known, however, about the molecular mechanisms by which these factors act.We have purified a 42-kDa glycoprotein from chicken brain, called ARIA (for AcChoR-inducing activity), that stimulates the rate of insertion of AcChoRs into the membrane of chicken myotubes by as much as 5-fold at picomolar concentrations (15). We were interested in determining which steps of receptor biosynthesis were altered by this factor. Synthesis of the AcChoR is a complex process consisting of transcription of the genes encoding each of the four receptor subunits, translation of the corresponding mRNAs, covalent and conformational modification of the polypeptide chains, assembly of the subunits into a pentameric complex, and transport to the cell surface (reviewed in ref. 16). We report here that the 42-kDa ARIA increases the level of mRNA encoding the a but not the 'y or 8 subunits of the AcChoR. MATERIALS AND METHODSCell Culture. Mononucleated cells were dissociated from pectoral muscles of 11-to 12-day-ol...

We examined a panel of 21 patients diagnosed with compulsive buying for two DNA sequence polymorphisms found in the gene that encodes the serotonin transport (5-HTT). One polymorphism, found in the promoter region of the 5-HTT gene, involves a 44-base pair (bp) deletion, and the other, found in the second intron, is due to variable numbers of a repeat sequence. We also typed a panel of 38 psychiatrically normal controls for both 5-HH markers. When compared to this control panel, no significant differences were seen for either 5-HTT marker among the compulsive buyers.

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The nucleotide sequence and chromosomal localization of a human pseudogene is reported. Sequence data suggest that this pseudogene was derived via reverse transcription from the gene encoding the cytosolic isoform of the enzyme serine hydroxymethyltransferase. In addition, a heteroduplex analysis of this pseudogene among several species of nonhuman primate indicates a relatively high degree of sequence conservation.

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