bromochloroacetic-acid and molybdenum-cofactor

Gephyrin is essential for both the postsynaptic localization of inhibitory neurotransmitter receptors in the central nervous system and the biosynthesis of the molybdenum cofactor (Moco) in different peripheral organs. Several alternatively spliced gephyrin transcripts have been identified in rat brain that differ in their 5' coding regions. Here, we describe gephyrin splice variants that are differentially expressed in non-neuronal tissues and different regions of the adult mouse brain. Analysis of the murine gephyrin gene indicates a highly mosaic organization, with eight of its 29 exons corresponding to the alternatively spliced regions identified by cDNA sequencing. The N- and C-terminal domains of gephyrin encoded by exons 3-7 and 16-29, respectively, display sequence similarities to bacterial, invertebrate, and plant proteins involved in Moco biosynthesis, whereas the central exons 8, 13, and 14 encode motifs that may mediate oligomerization and tubulin binding. Our data are consistent with gephyrin having evolved from a Moco biosynthetic protein by insertion of protein interaction sequences.

Topics: Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Brain; Carrier Proteins; Coenzymes; Cytoskeletal Proteins; Exons; Genetic Variation; Genomic Library; Humans; Introns; Keratins; Membrane Proteins; Metalloproteins; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Molybdenum Cofactors; Organ Specificity; Phylogeny; Pteridines; Rats; Sequence Alignment; Sequence Homology, Amino Acid