Biology subjects

Khallaf, M.

Publications and source records attributed to Khallaf, M..

3 recordsLinked to original sources

bioRxiv2024

TENM4 is an essential transduction component for touch and pain

Gentle touch is conveyed to the brain by fast-conducting sensory fibers. Mechanosensitive ion channels at the terminals of these neurons are thought to be gated by extracellular tethers that transmit force from the surrounding matrix to the channel complex, but the molecular identity of such tethers has remained unknown. Here, we identify Teneurin-4 (TENM4) as an essential extracellular linker protein for mechanotransduction in mechanoreceptors. Sensory neuron-specific deletion of Tenm4 in mice caused profound touch insensitivity, while acute and reversible proteolytic disassembly of TENM4 at sensory endings confirmed its direct role in force transduction. Ultrastructural analyses revealed TENM4 localization to filamentous structures at the neurite-laminin interface, defining it as a structural component of the mechanosensory tether. These findings identify TENM4 as a core element of fast somatic sensation and provide molecular insight into how extracellular forces are coupled to ion channel activation.

neuroscience↗

bioRxiv2024

Quantitive variation of male and female-specific compounds in 99 drosophilid flies

Variation in sex pheromones is regarded as one of the causes of reproductive isolation and speciation. We recently identified 51 male- and female-specific compounds - many of which function as sex pheromones - in 99 drosophilid species1. Here, we report that despite many of these compounds being shared between species, their quantities differ significantly. For example, although 34 drosophilid species share the male-specific compound cis-vaccenyl acetate (cVA), which plays a critical role in regulating various social and sexual behaviors, the amount of cVA can differ by up to 600-fold between different species. Additionally, we found 7-tricosene, the cuticular hydrocarbon pheromone, present in 35 Drosophila species. Our findings indicate that 7-tricosene is equally present in both sexes of 14 species, more abundant in males of 14 species, and more abundant in females of 7 species. We provide raw data on the concentration of potential pheromone components in the 99 drosophilids, which can provide important insights for further research on the behavior and evolution of these species. Quantitative variations highlight species-specific patterns, suggesting an additional mechanism for reproductive isolation built on specific combinations of compounds at set concentrations.

evolutionary biology↗

bioRxiv2023

Touch sensation requires the mechanically-gated ion channel Elkin1.

The slightest touch to the skin initiates tactile perception that is almost immediate1. The extraordinary speed of touch perception is enabled by mechanically-activated ion channels, the opening of which excites the endings of sensory neurons innervating the skin to initiate sensation. Here we identify a new mechanically-activated ion channel, Elkin12, that, when ablated in mice, leads to a profound behavioural touch insensitivity. Touch insensitivity in Elkin1-/- mice was caused by a loss of mechanically-activated currents (MA-currents) in around half of all sensory neurons that are activated by light touch (low threshold mechanoreceptors, LTMRs). Reintroduction of Elkin1 into sensory neurons from Elkin1-/- mice acutely restored MA-currents. Piezo23-6 is an established mechanosensitive ion channel required for touch sensation. In mice genetic ablation of Piezo2 renders many, but not all, LTMRs insensitive to mechanical force4,5,7. Here we show that Elkin1 underpins PIEZO2-independent touch sensation. Additionally, we find that Elkin1 is present in many nociceptive sensory neurons which detect potentially damaging and painful mechanical force. These nociceptors depend on Elkin1 for effectively communicating information on sustained noxious mechanical forces. We further identified molecular and functional interactions between the known mechanotransduction protein Stoml38,9 and Elkin1 ion channels. Our data identify Elkin1 as a novel core component of touch transduction in mammals. The specific sensory deficits exhibited by Elkin1-/- mice make Elkin1 a highly desirable target that could be harnessed to treat somatic sensory disorders including pain.

neuroscience↗