Biology subjects

Turner, H.

Publications and source records attributed to Turner, H..

3 recordsLinked to original sources

bioRxiv2021

Requirement for an Otopetrin-Like protein for acid taste in Drosophila

Many of the Drosophila receptors required for bitter, sugar and other tastes have been identified. However, the receptor required for the taste of acid has been elusive. In Drosophila, the major families of taste receptors, such as "Gustatory Receptors" and "Ionotropic Receptors" are unrelated to taste receptors in mammals. Previous work indicated that members of these major families do not appear to be broadly required acid sensors. Here, to identify the enigmatic acid taste receptor, we interrogated three genes encoding proteins distantly related the mammalian Otopertrin1 proton channel. We found that RNAi knockdown or mutation of Otopetrin-Like A (OtopLA) by CRISPR/Cas9, severely impairs the behavioral rejection of sugary foods laced with HCl or carboxylic acids. Mutation of OtopLA also greatly reduces acid-induced action potentials. We identified an isoform of OtopLA that was expressed in the proboscis and was sufficient to restore acid sensitivity to OtopLA mutant flies. OtopLA functioned in acid taste in a subset of bitter-activated gustatory receptor neurons that senses protons. This work highlights an unusual functional conservation of a receptor required for a taste modality in flies and mammals.

neuroscience↗

bioRxiv2021

A Non-redundant Role for T cell-derived IL-22 in Antibacterial Defense of Colonic Crypts

IL-22 is a key cytokine in immune defense against pathogens at barrier sites. In response to enteric attaching and effacing bacteria, IL-22 produced by type 3 innate lymphoid cells (ILC3s) is thought to be important early for induction of antimicrobial peptides (AMPs) that protect intestinal epithelial cells (IECs) in advance of T cell-derived IL-22 that arises later. Yet, the basis for a requirement for both innate and adaptive IL-22-producing immune cells in protecting the intestinal mucosa is unknown. Here, using novel mice that both report IL-22 expression and can be targeted for its lineage-specific deletion, we show that mice with deficiency of IL-22 targeted to innate immune cells, including ILC3s, have impaired STAT3 activation of surface colonic IECs colonized by bacteria early in infection. In contrast, mice with IL-22 deficiency limited to T cells have complete loss of STAT3 activation in IECs lining colonic crypts and fail to protect the crypts from bacterial invasion late despite ongoing production of IL-22 from ILC3s. T cell-derived IL-22 is required for upregulation of many host-protective genes by crypt IECs, including those encoding AMPs, neutrophil-recruiting chemokines, and mucins and mucin-related molecules, while also restricting pro-inflammatory genes downstream of IFN{gamma} and TNF signals. Thus, T cell-derived IL-22 is indispensable for antibacterial defense and damage control of intestinal crypts.

immunology↗

bioRxiv2021

A de novo paradigm for male infertility

IntroductionDe novo mutations (DNMs) are known to play a prominent role in sporadic disorders with reduced fitness1. We hypothesize that DNMs play an important role in male infertility and explain a significant fraction of the genetic causes of this understudied disorder. To test this hypothesis, we performed trio-based exome-sequencing in a unique cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare protein altering DNMs were classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of Loss-of-Function (LoF) DNMs in LoF-intolerant genes (p-value=1.00x10-5) as well as predicted pathogenic missense DNMs in missense-intolerant genes (p-value=5.01x10-4). One DNM gene identified, RBM5, is an essential regulator of male germ cell pre-mRNA splicing2. In a follow-up study, 5 rare pathogenic missense mutations affecting this gene were observed in a cohort of 2,279 infertile patients, with no such mutations found in a cohort of 5,784 fertile men (p-value=0.009). Our results provide the first evidence for the role of DNMs in severe male infertility and point to many new candidate genes affecting fertility.

genetics↗