repeats that code for histidine rich and glutamine rich regions close to the N and C terminal ends of the protein. Molecular analysis of ro has led to the discovery of a new homeo box-containing gene that is necessary for normal eye development and has a structure similar to other genes involved in embryonic pattern formation. The embryonic homeo box genes are thought to be transcriptional regulators that specify segment identity and tissue type in the developing embryo. It is interesting to speculate that ro participates in specifying cell type in the developing ommatidia by regulating transcription. REFERENCES Banerjee, U.; Renfranz, P.J.; Pollock, J.A.; and Benzer, S. Molecular characterization and expression of sevenless, a gene involved in neuronal pattern formation in the Drosophila eye. Cell 49(2):281-291, 1987. Bowtell, D.; Simon, M.; and Rubin, G.M. Nucleotide sequence and structure of the sevenless gene of Drosophila melanogaster. Genes and Development 2:620-634, 1988. Gehring, W.J. Homeo boxes in the study of development. Science 236(4806):12451252, 1987. Hafen, E.; Basler, K.; Edstroem, J.-E.; and Rubin, G.M. Sevenless, a cell-specific homeotic gene of Drosophila, encodes a putative transmembrane receptor with a tyrosine kinase domain. Science 236(4797):55-63, 1987. Ready, D.F.; Hanson, T.E.; Benzer, S. Development of the Drosophila retina, a neurocrystalline lattice. Developmental Biology 53(2):217-240, 1976. Tomlinson, A., and Ready, D.F. Cell fate in the Drosophila ommatidium. Developmental Biology 123(1):264-275, 1987. Tomlinson, A.; Bowtell, D.D.L.; Hafen, E.; and Rubin, G.M. Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila. Cell 51(1):143-150, 1987. Tomlinson, A.; Kimmel, B.; and Rubin, G.M. Rough, a Drosophila homeo box gene required in photoreceptors R2 and R5 for inductive interaction in the developing eye. Cell 55:771-784, 1988. Abstracts Channels and Receptors Brain GABAA and Nicotinic Receptors: E.A. Barnard MRC Molecular Neurobiology Unit, MRC Centre, Hills Road, Work in our and collaborating laboratories on the cloned cDNAs encoding the GABAA receptor will be reviewed. In this receptor, GABA gates an intrinsic anion channel. It has been purified from bovine brain and shown to contain a and ẞB subunits. It has been shown that the ẞ subunit carries the GABA recognition site and the a subunit the benzodiazepine site, which acts on the former with positive allostery, probably in an a2 ß2 structure. cDNAs encoding the a and ẞ subunits of this receptor have been cloned. Pure RNAs encoding the a and B subunits can be generated in vitro from the a and the ß cDNAs; if injected together into the Xenopus oocyte, these produce the functional receptor and ion channel. A deduced model for this receptor will be presented. Multiple subtypes of this receptor are known pharmacologically and have now been identified as arising from different genes. Their structural and functional differences are of interest. Genomic structures and chromosomal locations will also be considered. Some of the cDNAs encoding the subunits of neuronal nicotinic acetylcholine receptors have been analysed similarly, again with oocyte expression. These belong to the same super-family. Structural motifs common to both receptor types, and determinants of special functional attributes in each, provide insights into the general principles governing the ion-channel-containing receptors. # The Nicotinic Acetylcholine Receptor Steve Heinemann, Jim Boulter, Evan Deneris, John Connolly, Roger Papke, Etsuko Wada, Keiji Wada, #Marc Ballivet, Larry Swanson*, and Jim Patrick Molecular Neurobiology Laboratory, *Neural Systems Laboratory and Howard Hughes Medical Institute, The Salk Institute, P.O. Box 85800, San Diego, California 92138. Department of Biochemistry, University of Geneva, Geneva, Switzerland A family of genes coding for nicotinic acetylcholine receptors has been identified in mammals. One class of genes codes for receptors expressed in muscle. A second and larger class codes for a family of receptors expressed in nerve cells of the peripheral and central nervous systems. The existence of a large number of genes coding for neuronal nicotinic receptors and the fact that they are expressed throughout the brain suggests that the nicotinic receptor system is one of the major excitatory receptor systems in the brain. Expression studies in Xenopus oocytes have shown that the following combinations of subunits form functional nicotinic receptors: alpha2/beta 2; alpha3/beta2 and alpha4/beta2. Each of the three functional combinations of subunits forms a pharmacologically distinct subtype. In addition, each of the three alpha subunits has a unique distribution of expression in the brain, consistent with the proposal that they are part of three independent nicotinic receptor systems. The application of molecular biology to the nicotinic receptor system will make it possible to study this system in detail. This may lead to insight into nicotine addiction and the mood changes that accompany nicotine consumption. Behavioral studies have linked the nicotinic receptor system to learning and memory, which is intriguing given the finding that Alzheimer's patients have a deficiency in cortical nicotinic receptors. The existence of receptor subtypes and the availability of cDNA clones make it possible to design new drugs that are subtype specific. Molecular Studies of Voltage-Sensitive L.Y. Jan, D.M. Papazian, T.L. Schwarz, B.L. Tempel, L.C. Timpe, and Y.N. Jan Howard Hughes Medical Institute, Departments of Physiology and Potassium channels probably form the most diverse group of ion channels and are essential to the control of excitability in the nervous system. They influence the duration of action potentials and the amount of transmitter released by terminals, and have been implicated in learning. Recent cloning of the Shaker locus in Drosophila has revealed that at least four probable components of potassium channel (the A channel) are encoded at this locus by a family of alternatively spliced transcripts. Messenger RNA coding for any one of these four Shaker proteins is sufficient to direct the synthesis of functional A channels in Xenopus oocytes, though the kinetic properties of these A currents differ. Immunocytochemical and immunoblot analyses of the Shaker proteins showed that the molecular weights of these proteins are roughly as predicted from their coding sequences, and that they are located primarily in the neuropile region of the central nervous system. A homolog of Shaker has been isolated from a mouse brain cDNA library and contains regions that are extremely similar in their amino acid sequences to Shaker, these regions are probably conserved to preserve certain structures that are important for channel function. |