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A Ferrus

Publications and source records attributed to A Ferrus.

13 recordsLinked to original sources
PubMed2001

A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila.

A suppressor mutation, D53, of the held-up(2) allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up(2), including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human alpha-tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

Amino Acid Sequence↗
PubMed1990

Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster.

Mutations in the Shaker (Sh) locus of Drosophila melanogaster have differing effects on action potential duration and repolarization in neurons as well as on A-type K+ channels (IA) in muscle. The molecular basis of three exemplary Sh alleles (ShKS133, ShE62 and Sh5) has been identified. They are point mutations in the Sh transcription unit expressing aberrant voltage-gated A-type K+ channels. Replicas of each mutation have been introduced by in vitro mutagenesis into Sh cDNA. The expression of in vitro transcribed mutant Sh cRNA in Xenopus laevis oocytes reproduced the specific phenotypic traits of each Sh allele. The lack of IA in ShKS133 is due to a missense mutation within a sequence motif occurring in all hitherto characterized voltage-gated K+ channel forming proteins. The reduction of IA in ShE62 is due to a mutation in an AG acceptor site. The intervening sequence between exons 19 and 20 is not spliced in ShE62 RNA. As a consequence, ShE62 flies do not contain the full complement of Sh K+ forming proteins. Finally, the Sh5 mutation leads to an altered voltage dependence of K+ channel activation and inactivation as well as to an accelerated rate of recovery from inactivation. This is due to a missense mutation altering the amino acid sequence of the proposed transmembrane segment S5 of the Sh K+ channels. Segment S5 is located adjacently to the presumed voltage sensor of voltage-gated ion channels. The results explain the altered properties of excitable cells in Sh mutants and provide a general model for the possible role of A-type K+ channels in modulating action potential profiles.

Action Potentials↗
PubMed1990

Alternative Shaker transcripts express either rapidly inactivating or noninactivating K+ channels.

Two members of the Shaker K+ channel family designated ShA2 and ShD2 were characterized in the Xenopus oocyte expression system. The predicted amino acid sequences of ShA2 and ShD2 differ only in the amino terminus, which is located intracellularly according to the present topological model of K+ channels. The differing amino termini have profound effects on the electrophysiological and pharmacological properties of the K+ channel. Most markedly, the nature of the amino terminus determines whether the K+ channel mediates rapidly inactivating or noninactivating K+ currents. It also affects the 4-aminopyridine, tetraethylammonium, and charybdotoxin sensitivities of the K+ channels. These results suggest that the amino terminus of Shaker proteins affects K+ channel structures on both sides of the membrane.

4-Aminopyridine↗
PubMed1989

The interference of truncated with normal potassium channel subunits leads to abnormal behaviour in transgenic Drosophila melanogaster.

The Shaker locus of Drosophila melanogaster encodes a family of A-type potassium channel subunits. Shaker mutants behave as antimorphs in gene dosage tests. This behaviour is due to the production of truncated A-channel subunits. We propose that they interfere with the function of their normal counterpart by forming multimeric A-channel structures. This hypothesis was tested by constructing transgenic flies carrying a heat-inducible gene encoding a truncated A-type potassium channel subunit together with a normal wild type doses of A-type potassium channel subunits. The altered subunit leads at larval, pupal or adult stages to the transformation of wild type into Shaker flies. The transformed flies exhibited a heat-inducible abnormal leg shaking behaviour and a heat-inducible facilitated neurotransmitter release at larval neuromuscular junctions. By the overexpression of an aberrant A-channel subunit the normal behaviour of transgenic D. melanogaster can be altered in a predictable way.

Amino Acid Sequence↗
PubMed1988

Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila.

The Shaker locus of Drosophila contains a very large transcription unit. It is expressed predominantly in the nervous system by multiple, differential as well as alternative, splicing mechanisms into different, but functionally related proteins. The structure of the Shaker transcription unit and the properties of the encoded Shaker protein family provide a molecular basis for A channel diversity in excitable cells.

Amino Acid Sequence↗
PubMed1987

Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an I(A) channel transcript with homology to vertebrate Na channel.

We have cloned 215-kb DNA containing the maternal effect region (ME) of the Shaker gene complex (shC) at 16F of the Drosophila X chromosome. Five translocation and deletion breakpoints have been mapped on the cloned DNA allowing a correlation of the genetic map to transcription units. The ME region spans 100 kb. The genetic behavior of this region correlates with the occurrence of maternal RNAs in this part of the ShC. Two transcripts have been identified in the vicinity of chromosomal rearrangements which cause a Sh phenotype. These are a 4.5-kb transcript interrupted by T(x;2)B27 and a 2-kb transcript interrupted by T(X;3)Sh and T(X;Y)W32. The latter transcript is derived from a primary transcript which spans >65 kb genomic DNA. The cDNA-sequencing data show that this Shaker (I(A)channel) gene can encode a protein of 35 kd with three alpha-helical membrane-spanning sequences near its carboxyl terminus. These have a striking homology with membrane-spanning sequences of the vertabrate Na channel.

Journal Article↗
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↗
PubMed1975

Parameters of mitotic recombination in minute mutants of Drosophila melanogaster.

A sample of 16 Minutes, representing 12 loci distributed over all the chromosome arms and including 3 pairs of alleles and 4 deficiencies, has been studied with respect to several developmental and recombinational parameters. Cell marker mutants located in most of the chromosome arms were used to assess (1) spontaneous and X-ray-induced mitotic recombination frequencies of each Minute, and (2) clone sizes of the different cell marker clones. These parameters were analyzed both in the wing disc and in the abdominal histoblasts.--Whereas spontaneous frequencies are not affected by the presence of the Minutes studied, the different Minutes characteristically increase the frequency of recombination clones arising after X-irradiation. The recombinant clones which are M+/M+ are significantly larger than clones in the same fly which retain the M+/M+ condition. This is particularly striking in clones in the wing disc, slightly so in clones in the tergites. The occurrence of mitotic recombination in the fourth chromosomes is reported for the first time.--Chaeta length and developmental delay correlates with the recombinational parameters in different ways. Possible causal interrelationships of the different traits of the Minute syndrome are discussed.

Abdomen↗
PubMedDate not supplied

[Survey of infant mortality in Mirebalais, Haiti].

Infant mortality remains high in Haiti, at 74 deaths per 1,000 live births. In this study, we aimed to assess infant mortality in Mirebalais and to identify the associated risk factors. We carried out a census of pregnant women in Mirebalais, at the beginning of the study, over a three-week period. Twelve researchers visited the homes of the newborns to enroll the families in the study and to collect demographic data. Further visits were scheduled for two, four, six, nine and twelve months after birth. If the child died during this time, the investigator asked the mother about all the steps taken to prevent the death of the child, and an autopsy was carried out. The survey began on July 12 1994 and ended on December 31 1995. During that time, about 2,151 pregnant women were enrolled. Seven of these women died and 16 had abortions. In total, 2,069 children were born to the enrolled women. We enrolled 515 other children after birth or following referral by health workers or midwives. We therefore followed 2,584 children. We found that 10% of the mothers were aged between 15 and 19 years, 66.3% had had one to three pregnancies and 73% were entirely uneducated. The early neonatal mortality rate was 4.64 per 1,000 live births, late neonatal mortality was 6.96 per thousand and post-neonatal mortality was 45.6 per thousand live births. Diarrhea was responsible for 60% of the deaths and acute respiratory infections for 11%, these two causes accounting for 71% of the deaths of children aged 1 to 12 months. Thus, although infant mortality has decreased it remains high in Mirebalais, largely due to diarrhea and acute respiratory infections in the post-neonatal period.

Adolescent↗