High impact information on tipE

• Using a heat shock promoter to control tipE+ gene expression in transgenic flies, we demonstrate that tipE+ gene expression is required during pupal development to rescue adult paralysis [1].
• Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function [1].
• These results indicate that both the tip-E and sei loci are important in regulation of sodium current density in embryonic neurons [2].
• Expression of a tipE+ transgene, in tipE- neurons, restores repetitive firing to wild-type levels [3].
• Here we report that the majority of neurons in both wild-type and tipE mutant (tipE-) embryo cultures fire sodium-dependent action potentials in response to depolarizing current injection [3].

Biological context of tipE

• Germline transformation using a 42-kb cosmid clone and successively smaller subclones localized the tipE gene within a 7.4-kb genomic DNA segment [4].
• Cytogenetic and molecular localization of tipE: a gene affecting sodium channels in Drosophila melanogaster [4].
• Furthermore, the duration of the interstimulus interval necessary to fire a second full-sized action potential is significantly longer in single- versus multiple-spiking transgenic neurons, suggesting that a slow rate of recovery of sodium currents contributes to the decrease in repetitive firing in tipE- neurons [3].
• This phenotype is also rescued by expression of the tipE+ transgene [3].
• One such mutation is temperature-induced paralysis locus E (tipE), which has been shown by electrophysiology and ligand binding studies to reduce sodium channel numbers [4].

Anatomical context of tipE

• The Drosophila para sodium channel alpha subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit [5].
• A recessive temperature-sensitive paralytic mutation, tip-E, is associated with reduced binding of [3H]saxitoxin to voltage-sensitive sodium channels in membranes from adult Drosophila heads [6].

Associations of tipE with chemical compounds

• The pyrethroid insecticide cismethrin prolonged the sodium current carried by Vssc1/tipE sodium channels during a depolarizing pulse and induced a tail current after repolarization [7].
• Cypermethrin, a pyrethroid with Type II effects on intact nerve, also prolonged the inactivation of Vssc1/tipE sodium channels and induced a tail current [8].

Other interactions of tipE

• Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay [5].
• In the mutants tipE, napts and parats, conduction in certain neurons presynaptic to the CGF failed at about the same temperature at which paralysis occurred in each mutant [9].

Analytical, diagnostic and therapeutic context of tipE

• Recent progress in the cloning of alpha (para) and beta (TipE) Na channel sub-units from Drosophila melanogaster (fruit fly) and Musca domestica (housefly) have facilitated functional expression studies of insect Na channels in Xenopus laevis oocytes, assayed by voltage clamp techniques [10].

References