Biology subjects

Amrein, H.

Publications and source records attributed to Amrein, H..

3 recordsLinked to original sources

bioRxiv2024

Glucose-6-phosphatase is required for sperm energy metabolism, motility and fertility in Drosophila

Glucose-6-Phosphatase (G6Pase), a key enzyme in gluconeogenesis and glycogenolysis in the mammalian liver and kidney, converts glucose-6-phosphate to glucose for maintaining systemic blood glucose homeostasis during nutrient deprivation. However, its function has remained elusive in insects, which have no need for G6Pase in sugar homeostasis since they convert glucose-6-phosphate to trehalose, their main circulating sugar, via trehalose phosphate synthase (TPS1). In this study we identify an unexpected and essential requirement for G6Pase in Drosophila male fertility, specifically to produce motile sperm. In G6P mutant males, spermatogenesis and spermiogenesis appear to proceed normally, leading to the production and transfer of mature sperm. However, once inside the female reproductive tract, G6P mutant sperm exhibit severely reduced tail beat frequency and only rarely enter an egg. Moreover, when compared to wild type sperm, G6P-deficient sperm are depleted more rapidly from the spermatheca and seminal receptacle, the female sperm storage organs. Immunohistochemical analyses show that G6P mutant spermatocytes present with an enlarged and stressed endoplasmic reticulum (ER) and a diminished Golgi apparatus. Additionally, the acrosome, a Golgi derived organelle that is critical for sperm capacitation, exhibits diminished expression of the transmembrane protein SNEAKY, which is essential to breakdown the sperm plasma membrane after fertilization. Metabolic analyses show impairment of both basal and compensatory glycolysis, as well as ATP production, in testes of G6P mutant males. Taken together, our investigations unveil a novel and crucial function for G6Pase in male fertility, highlighting its importance in regulating energy homeostasis in reproductive tissues.

cell biology↗

bioRxiv2023

Drosophila Neuronal Glucose 6 Phosphatase is a modulator of Neuropeptide Release that regulates muscle glycogen stores via FMRFamide signaling

Neuropeptides (NPs) and their cognate receptors are critical effectors of diverse physiological processes and behaviors. We recently reported of a non-canonical function of the Drosophila Glucose-6-Phosphatase (G6P) gene in a subset of neurosecretory cells in the CNS that governs systemic glucose homeostasis in food deprived flies. Here, we show that G6P expressing neurons define 6 groups of neuropeptide secreting cells, 4 in the brain and 2 in the thoracic ganglion. Using the glucose homeostasis phenotype as a screening tool, we find that neurons located in the thoracic ganglion expressing FMRFamide neuropeptides (FMRFaG6P neurons) are necessary and sufficient to maintain systemic glucose homeostasis in starved flies. We further show that G6P is essential in FMRFaG6P neurons for attaining a prominent Golgi apparatus and secreting neuropeptides efficiently. Finally, we establish that G6P dependent FMRFa signaling is essential for the build-up of glycogen stores in the jump muscle which expresses the receptor for FMRFamides. We propose a general model in which the main role of G6P is to counteract glycolysis in peptidergic neurons for the purpose of optimizing the intracellular environment best suited for the expansion of the Golgi apparatus, boosting release of neuropeptides and enhancing signaling to respective target tissues expressing cognate receptors. SIGNIFICANCE STATEMENTGlucose-6-phosphtase (G6P) is a critical enzyme in sugar synthesis and catalyzes the final step in glucose production. In Drosophila - and insects in general - where trehalose is the circulating sugar and Trehalose phosphate synthase, and not G6P, is used for sugar production, G6P has adopted a novel and unique role in peptidergic neurons in the CNS. Interestingly, flies lacking G6P show diminished Neuropeptide secretions and have a smaller Golgi apparatus in peptidergic neurons. It is hypothesized that the role of G6P is to counteract glycolysis, thereby creating a cellular environment that is more amenable to efficient neuropeptide secretion.

neuroscience↗

bioRxiv2023

Opposing chemosensory functions of closely related gustatory receptors

Most animals have functionally distinct populations of taste cells, expressing receptors that are tuned to compounds of different valence. This organizational feature allows for discrimination between chemicals associated with specific taste modalities and facilitates differentiating between unadulterated foods and foods contaminated with toxic substances. In the fruit fly D. melanogaster, primary sensory neurons express taste receptors that are tuned to distinct groups of chemicals, thereby activating neural ensembles that elicit either feeding or avoidance behavior. Members of a family of ligand gated receptor channels, the Gustatory receptors (Grs), play a central role in these behaviors. In general, closely related, evolutionarily conserved Gr proteins are co-expressed in the same type of taste neurons, tuned to chemically related compounds, and therefore triggering the same behavioral response. Here, we report that members of the Gr28 subfamily are expressed in largely non-overlapping sets of taste neurons in Drosophila larvae, detect chemicals of different valence and trigger opposing feeding behaviors. We determined the intrinsic properties of Gr28 neurons by expressing the mammalian Vanilloid Receptor (VR1), which is activated by capsaicin, a chemical to which wildtype Drosophila larvae do not respond. When VR1 is expressed in Gr28a neurons, larvae become attracted to capsaicin, consistent with reports showing that Gr28a itself encodes a receptor for nutritious RNA. In contrast, expression of VR1 in two pairs of Gr28b.c neurons triggers avoidance to capsaicin. Moreover, neuronal inactivation experiments show that the Gr28b.c neurons are necessary for avoidance of several bitter compounds. Lastly, behavioral experiments of Gr28 deficient larvae and live Ca2+ imaging studies of Gr28b.c neurons revealed that denatonium benzoate, a synthetic bitter compound that shares structural similarities with natural bitter chemicals, is a ligand for a receptor complex containing a Gr28b.c or Gr28b.a subunit. Thus, the Gr28 proteins, which have been evolutionarily conserved over 260 million years in insects, represent the first taste receptor subfamily in which specific members mediate behavior with opposite valence.

neuroscience↗