Biology subjects

Ramos, C. I.

Publications and source records attributed to Ramos, C. I..

5 recordsLinked to original sources

bioRxiv2025

Symbiosis through lysis: prophage activation underlies Lactiplantibacillus plantarum probiotic function

The release of bacterial bioactive molecules across the gut barrier is a crucial yet poorly understood step in microbe-host molecular dialog. Here we unravel a phage-driven mechanism that enables this process in a symbiont that supports host adaptive growth. In Lactiplantibacillus plantarum NC8 (LpNC8), we identify a stress-inducible prophage, pp2, that undergoes genotoxic-stress-dependent activation in vivo and triggers holin-lysin-mediated lysis. This controlled lytic program produces phage particles together with extracellular vesicles (EVs), enriched in symbiotic cues, including lipoteichoic acids. In a model of beneficial symbiosis, pp2-dependent lysis is strictly required for the ability of LpNC8to support juvenile growth in nutritionally challenged Drosophila melanogaster. Disruption of pp2-dependent lysis abolishes EVs release in vitro and alters the growth-promoting effect in vivo. We show that the acidic region of the Drosophila midgut, but not host antimicrobial peptides nor lysozymes, acts as a physiological trigger of prophage induction: removal of this acidic compartment markedly reduces phage production and impairs LpNC8-mediated growth promotion. These findings demonstrate that host gut physiology regulates prophage activation and reveal prophage-induced lysis as a previously unrecognized mechanism by which a beneficial gut bacterium releases symbiotic cues to support host development during nutritional stress.

microbiology↗

bioRxiv2025

A nutrient-sensitive enterokine coordinates developmental plasticity through inter-organ signalling

Animal survival in fluctuating environments depends on the ability to modulate their developmental pace in response to nutrient availability, a phenomenon known as developmental plasticity. In Drosophila larvae, we uncover a critical endocrine mechanism that coordinates this process under conditions of amino acid restriction. We identify the peptide hormone Limostatin as an enterokine, produced by a small population of larval midgut enteroendocrine cells, that acts systemically to inhibit the expression and release of dIlp2, a major insulin-like peptide controlling developmental progression. Limostatin expression and secretion by enteroendocrine cells is triggered by reduced amino acid availability through an inter-organ relay involving the fat body and neuroendocrine insulin-producing cells in the brain. In turn, Limostatin participates in a feedback control loop that slows down developmental progression once systemic nutrient shortage is sensed. This bidirectional gut-brain axis enables larvae to preserve viability under nutritional stress. Our findings define the larval gut as a nutrient-sensitive endocrine organ and position Limostatin as a key regulator of developmental plasticity. Our work expands the concept of decretins to include developmental pace control, suggesting that enterokines that regulate IGF signalling, rather than insulin release per se, may represent an evolutionarily conserved or convergent strategy in regulating developmental plasticity.

developmental biology↗

bioRxiv2025

Drosophila larval gut transcriptome reveals a microbe-mediated intestinal tissue growth via Ecdysone during adaptive growth

Organ and systemic growth must remain coordinated during development, even under nutritional stress. In Drosophila larvae, the intestinal microbiota contributes to this coordination by promoting growth and maturation under chronic undernutrition. Using gnotobiotic models, we show that association with Lactiplantibacillus plantarum (Lp) selectively enhances midgut growth relatively to other organs, providing an adaptive mechanism that buffers the impact of dietary restriction. Transcriptomic profiling of larval midguts revealed a strong Ecdysone signaling signature upon Lp association. Functional analyses showed that local conversion of Ecdysone to its active form, 20-hydroxyecdysone, by the cytochrome P450 enzyme Shade, together with enterocyte Ecd receptor activity, is required for Lp-dependent intestinal and systemic growth. Pharmacological activation of Ecd signaling partially mimicked the bacterial effect, confirming its sufficiency to drive adaptive midgut expansion. Our results uncover an unexpected role of intestinal Ecd signaling in microbiota-driven developmental plasticity, revealing how commensal bacteria modulate local steroid signaling to fine-tune organismal growth and maturation.

cell biology↗

bioRxiv2024

Neto proteins differentially modulate the gating properties of Drosophila NMJ glutamate receptors

The formation of functional synapses requires co-assembly of ion channels with their accessory proteins which controls where, when, and how neurotransmitter receptors function. The auxiliary protein Neto modulates the function of kainate-type glutamate receptors in vertebrates as well as at the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse widely used for genetic studies on synapse development. We previously reported that Neto is essential for the synaptic recruitment and function of glutamate receptors. Here, using outside-out patch-clamp recordings and fast ligand application, we examine for the first time the biophysical properties of recombinant Drosophila NMJ receptors expressed in HEK293T cells and compare them with native receptor complexes of genetically controlled composition. The two Neto isoforms, Neto- and Neto-{beta}, differentially modulate the gating properties of NMJ receptors. Surprisingly, we found that deactivation is extremely fast and that the decay of synaptic currents resembles the rate of iGluR desensitization. The functional analyses of recombinant iGluRs that we report here should greatly facilitate the interpretation of compound in vivo phenotypes of mutant animals.

neuroscience↗

bioRxiv2019

Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction

Glutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and post-synaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology and electrophysiology we demonstrate that Neto- functions on both sides of the NMJ. In muscle, Neto- limits the size of the postsynaptic receptors field. In motor neurons, Neto- controls neurotransmitter release in a KAR-dependent manner. Furthermore, Neto- is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto- is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensured NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.

neuroscience↗