We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat-number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD.

Recently, we isolated cDNAs for the TXA2 receptor (15, 16) and the EP1 (17), the EP2 (18), and the EP3 (19,20) subtypes ofthe PGE receptors by homology screening. These studies revealed that prostanoid receptors constitute a subfamily within the rhodopsin-type, G protein-coupled receptor superfamily (21), and they enabled us to identify highly conserved amino acid sequences in these receptors. To clone the cDNAs for other prostanoid receptors, we have carried out reverse transcription polymerase chain reaction (RT-PCR) studies based on such motifs and have successfully amplified three cDNAs encoding sequences homologous to prostanoid receptors. Of these three, one has been identified as being part of the PGF receptor cDNA (22) and another as being part of the PG1 receptor cDNA (23). The third, unidentified, cDNA showed a high degree ofsequence similarity to the PGI receptor (23) and to the EP2 subtype of the PGE receptor (18). We postulated that the cDNA may code for a member ofthe relaxant prostanoid receptor family. Here, we report the primary structure of this mouse cDNA and its gene.t We also describe the identification ofthe gene product MATERIALS AND METHODS Lgands. PGD2, PGE2, PGF2a, and STA2 (9,11-epithio-11,12-methano-TXA2) were kindly provided by Ono Pharmaceuticals (Osaka). BW 245C [5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin] and BW A868C

Background: Rab small GTPases are membrane trafficking proteins in eukaryotes. Results: Comprehensive knockdown screening identified six Rab isoforms that are involved in regulating Golgi morphology in HeLa-S3 cells. Conclusion: Five of the six Rabs, including Rab2A and Rab2B, non-redundantly regulate Golgi morphology. A Rab2B-specific effector, GARI-L4, also regulates it. Significance: This is the first study to systematically analyze all human Rabs in the Golgi.