Biology subjects

Munneke, A. S.

Publications and source records attributed to Munneke, A. S..

3 recordsLinked to original sources

bioRxiv2024

Cell non-autonomous signaling through the conserved C. elegans glycopeptide hormone receptor FSHR-1 regulates cholinergic neurotransmission

Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored. Glycoproteins and their G protein-coupled receptors (GPCRs) are well-established orchestrators of multi-tissue signaling events that govern diverse physiological processes through both cell-autonomous and cell non-autonomous regulation. Here, we show that follicle stimulating hormone receptor, FSHR-1, the sole Caenorhabditis elegans ortholog of mammalian glycoprotein hormone GPCRs, is important for cell non-autonomous modulation of synaptic transmission. Inhibition of fshr-1 expression reduces muscle contraction and leads to synaptic vesicle accumulation in cholinergic motor neurons. The neuromuscular and locomotor defects in fshr-1 loss-of-function mutants are associated with an underlying accumulation of synaptic vesicles, build-up of the synaptic vesicle priming factor UNC-10/RIM, and decreased synaptic vesicle release from cholinergic motor neurons. Restoration of FSHR-1 to the intestine is sufficient to restore neuromuscular activity and synaptic vesicle localization to fshr-1-deficient animals. Intestine-specific knockdown of FSHR-1 reduces neuromuscular function, indicating FSHR-1 is both necessary and sufficient in the intestine for its neuromuscular effects. Re-expression of FSHR-1 in other sites of endogenous expression, including glial cells and neurons, also restored some neuromuscular deficits, indicating potential cross-tissue regulation from these tissues as well. Genetic interaction studies provide evidence that downstream effectors gsa-1/GS, acy-1/adenylyl cyclase and sphk-1/sphingosine kinase and glycoprotein hormone subunit orthologs, GPLA-1/GPA2 and GPLB-1/GPB5, are important for FSHR-1 modulation of the NMJ. Together, our results demonstrate that FSHR-1 modulation directs inter-tissue signaling systems, which promote synaptic vesicle release at neuromuscular synapses.

neuroscience↗

bioRxiv2021

Serotonin and dopamine modulate aging in response to food perception and availability

An organisms ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction (DR), acts in-part through a cell non-autonomous signaling pathway that is inhibited by the perception of attractive smells. Using an intestinal reporter for a key gene induced by DR but suppressed by attractive smells, we identify three compounds that block food perception in C. elegans, thereby increasing longevity as DR mimetics. These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food perception. We further identify an enteric neuron in this pathway that signals through the serotonin receptor 5-HT1A/ser-4 and dopamine receptor DRD2/dop-3. Aspects of this pathway are conserved in D. melanogaster and mammalian cells. Thus, blocking food perception through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction.

molecular biology↗

bioRxiv2019

Perception of naturally dead conspecifics impairs health and longevity through serotonin signaling in Drosophila

Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. In humans, psychological trauma is often associated with the recognition of dead individuals, with chronic exposure leading to persistent mental health issues including depression and post-traumatic stress disorder. The mechanisms that link mental and physical health, and the degree to which these are shared across species, remain largely unknown. Here we show that the vinegar fly, Drosophila melanogaster, has the capability to perceive dead conspecifics in its environment and that this perceptive experience induces both short- and long-term effects on health and longevity. Death perception is mediated by visual and olfactory cues, and remarkably, its effects on aging are eliminated by targeted attenuation of serotonin signaling. Our results suggest a complex perceptive ability in Drosophila that reveals deeply conserved mechanistic links between psychological state and aging, the roots of which might be unearthed using invertebrate model systems.

animal behavior and cognition↗