Biology subjects

Reiter, E.

Publications and source records attributed to Reiter, E..

10 recordsLinked to original sources

bioRxiv2026

Spatiotemporal Modeling of GPCR Signaling: The Role of Endosomal Dynamics and Receptor Recycling

Cells communicate via extracellular ligands, such as hormones, which bind to plasma membrane receptors and trigger intracellular signaling cascades. G Protein-Coupled Receptors (GPCRs) exemplify this mechanism by initiating signaling both at the cell surface and, from intracellular compartments such as endosomes. The kinetics and spatial localization of these signals are critical determinants of cellular responses, yet receptor trafficking-including internalization, endosomal sorting, and recycling-remains a pivotal but often overlooked component of theoretical GPCR models. In this study, we present a mathematical framework that integrates receptor trafficking and signaling compartmentalization into generic GPCR dynamic models. Using a compartmentalized approach based on systems of ordinary differential equations (Chemical Reaction Networks), we analyze how receptor internalization and recycling modulate ligand-induced responses. Our results show that the balance between plasma membrane and endosomal signaling can significantly enhance or diminish ligand efficacy. Calibrated with high-throughput kinetic data, our model offers a refined tool for ligand pharmacological characterization and advances the understanding of GPCR signaling spatial organization.

systems biology↗

bioRxiv2026

Using herbarium genomics to understand the history of a global plant invasion

Invasive plants are dynamic eco-evolutionary systems characterized by rapid spread and evolutionary change. Herbarium genomics offers a powerful way to study these processes across broad spatial and temporal scales. We generated low-coverage shotgun-sequencing data from 152 herbarium specimens of the invasive Japanese knotweed species complex (Reynoutria), collected across its native range in Japan and China, and its introduced ranges in Europe and North America, spanning 200 years of global spread. Introduced populations of R. japonica, R. japonica var. compacta and R. sachalinensis showed reduced genetic diversity compared to native populations and were genetically most similar to Japanese specimens, indicating Japan as the source of all three introductions. European and North American R. japonica were genetically highly similar and closely related to local R. x bohemica hybrids, suggesting that these hybrids originated post-introduction, through hybridization and subsequent introgression from the R. japonica parent. A few R. x bohemica hybrids in the UK and France shared a multilocus lineage with R. sachalinensis, indicating an independent but ecologically less successful hybridization event involving introgression from R. sachalinensis. A genetically distinct R. x bohemica from Japan was closely related to a Japanese R. sachalinensis specimen, suggesting that hybridization also occurs in the native range. Introduced R. japonica has remained genetically uniform for [~]200 years reflecting long-term founder effects. The dominance of a single R. japonica lineage supports the general-purpose genotype hypothesis and the importance of vegetative reproduction in its spread. Herbarium genomics thus uncovers the origin and global spread of Japanese knotweed, providing direct molecular evidence of long-term plant invasions.

evolutionary biology↗

bioRxiv2025

The shared genomic history of Middle to Late Holocene Southern Cone populations

The Southern Cone represents the southernmost region of South America to be colonized by humans. Although ancient genomes have been sequenced from southern Patagonia, genomic data from the central Southern Cone remain temporally and spatially sparse. The archaeological record of this region documents major cultural transformations during the Middle and Late Holocene, yet their relationship to demographic processes has long been debated. Here, we present genome-wide data from 52 individuals spanning the past 5,000 years, originating from four regions of the central Southern Cone in present-day Argentina and Uruguay: the central and southern Pampas, Northwest Patagonia, the Parana River Delta and Lower Uruguay River, and the eastern lowlands of Uruguay. Genomic evidence from the Pampas reveals the presence of at least three distinct ancestries during the Middle Holocene. While genetic contacts with southern Patagonian groups were sporadic, we identify the expansion of an ancestry of unknown geographic origin by 4,800 years ago, which increased substantially during the Late Holocene. This same ancestry arrived in Northwest Patagonia by at least 600 years ago, and it co-existed with individuals carrying a southern Andean genetic profile until colonial times. Genetic structure differentiates populations along the Parana River Delta and the Lower Uruguay River by approximately 1,600 years ago. In contrast, individuals from the eastern lowlands of Uruguay show genetic links with Sambaqui-associated populations from the southern coast of Brazil, suggesting the role of human dispersals in connecting tropical lowland cultural traditions. Overall, our work documents the diffusion of genetically distinct groups across all regions studied and provides compelling evidence that large-scale human movements contributed to the remarkable cultural diversity of central Southern Cone populations during the Middle and Late Holocene.

genetics↗

bioRxiv2025

LHR and Gαs trafficking drive sustained cAMP signalling from endosomes to control steroidogenesis

1.A growing number of G protein-coupled receptors (GPCRs) signal through G proteins from intracellular compartments following endocytosis. While for few receptors the physiological relevance of such mechanism has been established, the relationships between the spatio-temporal organization of cellular signalling and the physiological responses are still to be elucidated for most receptors. Signalling by the luteinizing hormone receptor (LHR) is essential to regulate sex steroids production in gonads, but how G protein-dependent signals from endosomes are functionally important for steroidogenesis remains unexplored. Here, we demonstrate that transient LHR activation promotes a prolonged Gs/cAMP signalling from endosomes, which requires ligand-induced independent receptor and Gs trafficking. We show that endosomal trafficking is specifically required for ligand-induced cAMP accumulation in the nucleus and gene expression, as well as for steroids production in Leydig cells. Thus, this study contributes to further understand the molecular mechanisms by which LHR, through signalling compartmentalization, controls gonadal steroidogenesis.

cell biology↗

bioRxiv2025

A single domain intrabody as a novel tool to bias the subcellular trafficking of the follicle-stimulating hormone receptor

Intracellular variable fragments from heavy-chain only antibodies of camelids (intra-VHH) have been successfully used for their stabilizing properties to solve the 3D structure of active G protein-coupled receptors (GPCRs) bound to their cognate transducers. They also provide tools to link a given conformation of a GPCR to the signalling network engaged, thus allowing extensive structure/activity studies. Recently, they have been instrumental in tracking active GPCRs in various subcellular compartments. Here, we report the isolation and characterization of iPRC2, an intra-VHH recognizing the 1st and 3rd intracellular loops of the FSHR, but not of the luteinizing hormone/choriogonadotropin receptor close relative. Its expression in the cell decreases the cAMP production in response to hormone binding, and requires Gs for optimal interaction with the receptor. Importantly, iPRC2 increases the FSHR accumulation in the early endosomes, and consequently, diminishes its recycling to the cell surface. Hence, in contrast to previously described intra-VHH that disclose active GPCR intracellular location, iPRC2 provokes per se a location bias, through its ability to reroute the FSHR. Thus, it is an innovative tool to examine the functional consequences of GPCR accumulation in various sub-cellular compartments.

pharmacology and toxicology↗

bioRxiv2024

A haplotype-based evolutionary history of barley domestication

Barley is an old crop with a complex history. Its evolution and the molecular basis of domestication have been intensely studied. This research has ruled out a single origin of the crop and motivated a model of mosaic genomics ancestry. As more and better genome sequences have become available, this concept can be refined: where do the building blocks of the mosaic, that is, the haplotypes come from? Were all cultivated barleys created equal or did some wild barley populations contribute more to some domesticated lineages? To answer these and other questions, we pursue a haplotype-based approach to connect diversity and population structure in wild and domesticated barley. We sequence the genomes of 628 genebank accessions and 23 archaeological specimens. Using these data, we infer the spatiotemporal origins of haplotypes and map the contributions of different wild barley populations either during the initial phase of domestication or through later gene flow. Ancient DNA sequences corroborate our genome-wide analysis in present-day samples. Our results indicate that an early domesticated founder population formed in the Fertile Crescent during an extended period of pre-domestication cultivation. A practical implication of our findings is that the high haplotype differentiation between barley populations, which arose possibly without, and most likely on top of, selective forces, complicates the mapping of adaptive loci.

plant biology↗

bioRxiv2024

Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells

The effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major impact on FSH-induced mRNA recruitment to the polysomes, since FSH stimulation promoted the release of polysome-enriched mRNAs, while mRNAs that were the least associated to polysomes were preferentially recruited to polysomes upon stimulation. The FSH signal did not alter the core biological functions of Sertoli cells, but shifted the proteins involved in these functions, suggesting a molecular rewiring of the FSH-induced gene expression. These findings underscore how ribosomal reallocation dynamically adapts the cellular translatome to microenvironmental changes, enabling cells to fine-tune protein production in response to external stimuli. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/629416v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@27334forg.highwire.dtl.DTLVardef@199c630org.highwire.dtl.DTLVardef@a28b92org.highwire.dtl.DTLVardef@1794172_HPS_FORMAT_FIGEXP M_FIG C_FIG Bullet points* In Sertoli cells, most mRNAs distribute similarly between monosomes and polysomes, but a sub-population is specifically enriched in polysomes * Basal polysomal enrichment level has a major impact on FSH-induced mRNA recruitment or release from the polysomes * The FSH signal induced a global rewiring of the proteins involved in Sertoli cell basal activity * FSH-induced reassignment of ribosomes to specific mRNAs has to comply with a tightly maintained mRNA distribution landscape

systems biology↗

bioRxiv2023

A single domain intrabody targeting the follicle-stimulating hormone receptor (FSHR) impacts FSH-induced G protein-dependent signalling

Intracellular variable fragments from heavy-chain antibody from camelids (intra-VHH) have been successfully used as chaperones to solve the 3D structure of active G protein-coupled receptors bound to their transducers. However, their effect on signalling has been poorly explored, although they may provide a better understanding on the relationships between receptor conformation and activity. Here, we isolated and characterized iPRC1, the first intra-VHH recognizing a member of the large glycoprotein hormone receptors family, the follicle-stimulating hormone receptor (FSHR). This intra-VHH recognizes the FSHR 3rd intracellular loop and decreases cAMP production in response to FSH, without altering Gs recruitment. Hence, iPRC1 behaves as an allosteric modulator and provides a new tool to complete structure/activity studies performed so far on this receptor.

pharmacology and toxicology↗

bioRxiv2020

Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor heteromeric complexes promote human ovarian follicle survival

Classically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradicting in vitro suggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the G{beta}{gamma} dimer while heteromer impairment or GPER-associated Gs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation. One Sentence SummaryFSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.

physiology↗

bioRxiv2019

Geographically structured genomic diversity of non-human primate-infecting Treponema pallidum subsp. pertenue

BackgroundIncreasing evidence suggests many non-human primate (NHP) species in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue (TPE), the bacterium causing yaws in humans. In humans, yaws is characterized by lesions of the extremities and face, while Treponema pallidum subsp. pallidum (TPA) causes venereal syphilis and is characterized by primary lesions on the genital, anal or oral mucosae, and has not been detected in NHPs. Due to a paucity of genetic data, it remains unclear whether other Treponema pallidum (TP) subspecies found in humans also occur in NHP and how the genomic diversity of TPE lineages that do occur in NHPs is distributed across hosts and space. MethodologyWe observed a combination of yaws- and syphilis-like symptoms in sooty mangabeys (Cercocebus atys atys) in Tai National Park (TNP), Cote dIvoire and collected swabs and biopsies from symptomatic animals. We also collected NHP bones from eight species from TNP, as well as from 19 species at 12 field sites across sub-Saharan Africa. Samples were screened for TP DNA using PCRs. In-solution hybridization capture coupled with high throughput sequencing was used to sequence TP genomes from positive samples. Principal findingsWe generated four nearly complete TP genomes from biopsies and swabs and five partial genomes from bones. Phylogenomic analyses revealed that both syphilis- and yaws-like lesions of sooty mangabeys within a single social group in TNP were caused by TPE. All TPE genomes determined from these sooty mangabeys were different and exhibited divergence levels not observed in TPE from a single species at any other field site where the disease seems to be epizootic. In general, simian TPE isolates did not form monophyletic clades based on host species or the type of symptoms caused by an isolate, but rather clustered based on geography. ConclusionsThere is a large diversity of TPE strains infecting NHPs in TNP. Our observations within a single social group of sooty mangabeys do not support the epizootic spread of a single clone, but rather points towards frequent independent introductions of the bacterium, which can cause syphilis- and yaws-like lesions. On a larger scale, the geographic clustering of TPE genomes might be compatible with cross-species transmission of TPE within ecosystems or environmental exposure leading to acquisition of closely related strains. Authors summaryIndividuals in several populations of wild non-human primates (NHP) in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue (TPE), a pathogen causing yaws disease in humans. In humans, yaws is characterized by skin lesions of the extremities and face. In contrast, Treponema pallidum subsp. pallidum, which causes venereal syphilis in humans, has not been observed in NHPs. We describe a combination of yaws- and syphilis-like symptoms in a sooty mangabey (Cercocebus atys atys) social group in Tai National Park (TNP), Cote dIvoire. We sampled lesioned animals and collected and tested NHP bones from field sites across sub-Saharan Africa. We were able to reconstruct four genomes from swabs/biopsies and five partial genomes from bone samples. Phylogenomic analyses revealed that syphilis-like lesions and yaws-like lesions in TNP were caused by a large diversity of TPE strains. Additionally, simian TPE isolates did not form monophyletic clades based on the host species or the types of symptoms caused by an isolate, but rather clustered by geographic origin. This is suggestive of cross-species transmission of TPE within ecosystems or environmental exposure leading to acquisition of closely related strains.

genomics↗