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M A Tanouye

Publications and source records attributed to M A Tanouye.

27 records · Page 2Linked to original sources
PubMed1988

Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity.

K+ channels are known through electrophysiology and pharmacology to be an exceptionally diverse group of channels. Molecular studies of the Shaker (Sh) locus in Drosophila have provided the first glimpse of K+ channel structure. The sequences of several Sh cDNA clones have been reported; none are identical. We have isolated and examined 18 additional Sh cDNAs in an attempt to understand the origin, extent, and significance of the variability. The diversity is extensive: we have already identified cDNAs representing at least nine distinct types, and Sh could potentially encode 24 or more products. This diversity, however, fits a simple pattern in which variable 3' and 5' ends are spliced onto a central constant region to yield different cDNA types. These different Sh cDNAs encode proteins with distinct structural features.

Amino Acid Sequence↗
PubMed1988

A-type potassium channels expressed from Shaker locus cDNA.

A-type K+ currents are expressed in Xenopus oocytes injected with in vitro-synthesized transcripts from cDNAs for the Drosophila Shaker (Sh) locus. A single Sh gene product, possibly as a multimer, is sufficient for formation of functional A channels. Various Sh RNAs express A currents with distinct kinetic properties. An analysis of structure-function relationships shows that the conserved central region of Sh polypeptides determines ionic selectivity and overall channel behavior, whereas the divergent amino and carboxyl termini can modify channel kinetics. Alternative splicing of Sh gene transcripts may provide one mechanism for the generation of K+ channel diversity.

Animals↗
PubMed1987

Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel.

The Drosophila Shaker (Sh) gene appears to encode a type of voltage-sensitive potassium (K+) channel called the A channel. We have isolated Sh as part of a 350 kb chromosomal walk. The region around Sh contains four identified transcription units. We find that Sh corresponds to a very large transcription unit encompassing a total of about 95 kb of genomic DNA and split by a major 85 kb intron. Sh has multiple hydrophobic domains that have a high probability of being membrane-spanning, consistent with the proposal that it encodes an ion channel.

Amino Acid Sequence↗
PubMed1985

Action potentials in normal and Shaker mutant Drosophila.

Intracellular microelectrode recordings from the cervical giant fiber of normal Drosophila show a characteristic action potential waveform for this identified neuron. The action potential has a rapid initial spike followed by a prominent depolarizing afterpotential. Pharmacological experiments suggest that the giant fiber action potential depends on inward currents carried by Na+ and outward currents carried by K+. Abnormal action potentials are seen in Shaker (Sh) mutant Drosophila. This study compares the effects of six Sh alleles. In each case, abnormalities are limited to action potential repolarization. There are, however, allelic differences. Five alleles cause delayed repolarization and increased action potential durations. Going from most to least extreme, these alleles are: Sh102 greater than ShKS133 greater than ShM greater than ShE62 greater than ShrKO120. Compared to normal action potentials, durations in the extreme mutants are longer by an order of magnitude or more. One mutant allele, Sh5 appears to cause an incompletely repolarized action potential, rather than a repolarization delay.

Action Potentials↗
PubMed1981

The morphology of the cervical giant fiber neuron of Drosophila.

The morphology of the cervical giant fiber (CGF) neuron of Drosophila melanogaster was studied by intracellular injection of Lucifer yellow dye. The CGF neuron is the command cell in a motor circuit causing visually driven escape behavior: a single action potential in a CGF axon produces patterned activity in jump and flight muscles. The present study identified the CGF cell body, a large soma located in the posterior part of the lower ipsilateral protocerebrum. The main process runs anteriorly from the cell body, extends three branches, and turns posteromedially while descending through the brain. The CGF axon courses through the cervical connective and ends within the mesothoracic neuromere of the thoracic ganglion. Thus, the CGF neuron is an interneuron, not a motoneuron as previously believed. We have been isolating mutants that affect CGF neuron-mediated behavior. Comparison of CGF neuron morphology in wildtype strains with that in these mutants will allow identification of genes that affect the development, structure, and connections of the CGF neuron.

Action Potentials↗
PubMed1981

Abnormal action potentials associated with the Shaker complex locus of Drosophila.

Intracellular recordings of action potentials were made from the cervical giant axon in Shaker (Sh) mutants and normal Drosophila. The mutants showed abnormally long delays in repolarization. The defect is not due to abnormal Ca(2+) channels, because it persists in the presence of Co(2+), a Ca(2+)-channel blocker. On the other hand, the K(+)-channel blocker 4-aminopyridine causes a similar effect in normal animals, suggesting that the Sh mutant may have abnormal K(+) conductance. Gene-dosage analysis of Sh shows that the defect is not due to underproduction of an otherwise normal molecule; it may be due to an abnormal molecule produced by the mutated gene. Gel electrophoresis failed to detect an abnormal protein, suggesting that, if Sh codes for a nervous system protein, it is rare. Genetic analysis of the Sh locus indicates three regions. Mutations or chromosome breaks in the two flanking regions cause Sh mutant physiology; the central region shows a "haplolethal effect"-i.e., heterozygous females are lethal.

Journal Article↗