Biology subjects

Augustin, S.

Publications and source records attributed to Augustin, S..

8 recordsLinked to original sources

bioRxiv2026

Vagal Signaling Decline in Age-related Macular Degeneration Drives Spleen-Dependent Retinal Inflammation

Under relaxed physiological conditions, vagal innervation via the splenic nerve restrains the release of inflammatory cytokines from splenic macrophages and helps preserve systemic homeostasis, constituting the efferent cholinergic anti-inflammatory arm of the inflammatory reflex. Our analysis of Danish National Patient Registry data revealed that vagotomy for peptic ulcer disease, particularly truncal vagotomy, markedly increased the risk of developing age-related macular degeneration (AMD). Consistently, experimental truncal vagotomy or splenic denervation in mice exacerbated laser- and light-induced subretinal inflammation, both models of late AMD. The pro-inflammatory effects of vagotomy were abolished by concurrent splenectomy or pharmacologically augmenting acetylcholine signaling. Mechanistically, vagotomy activated a pro-inflammatory transcriptional program in splenic monocytes while suppressing tissue-retention genes Cxcr4 and Fn1, leading to enhanced monocyte egress from the spleen and increased infiltration into the injured retina. In the laser-injured retina, single-cell RNA sequencing (scRNAseq) of mononuclear phagocytes revealed a broad set of vagotomy-induced transcripts in infiltrating monocytes and activated microglia. Remarkably, more than one-third of these were normalized by splenectomy. Together, these findings identify a vagus nerve-spleen-retina axis that connects stress and vagal tone to AMD pathogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/703339v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@677032org.highwire.dtl.DTLVardef@f6fc78org.highwire.dtl.DTLVardef@1393d3dorg.highwire.dtl.DTLVardef@e39a7a_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefUsing population-level human data and complementary mouse models, this study demonstrates that loss of vagal signaling enhances subretinal inflammation and increases susceptibility to age-related macular degeneration (AMD). Mechanistically, vagotomy reprograms splenic monocytes toward a pro-inflammatory state, promoting their egress and infiltration into the injured retina, where they amplify local inflammation. These effects identify a vagus nerve-spleen-retina axis that links reduced vagal tone to AMD pathogenesis. HighlightsO_LIVagotomy increases AMD risk in humans and exacerbates subretinal inflammation in mouse models of late-stage AMD. C_LIO_LILoss of vagal signaling drives pro-inflammatory reprogramming and enhanced egress of splenic monocytes via suppression of tissue-retention genes. C_LIO_LISingle-cell transcriptomics reveals vagotomy-induced inflammatory signatures in retinal monocytes and microglia that are largely reversed by splenectomy. C_LI

immunology↗

bioRxiv2025

Integration of auxin and cytokinin signalling in Arabidopsis root meristem maintenance through the secreted peptide CLE40

Plant meristems perpetually generate new cells for the initiation, growth and differentiation of various cell types and organs. CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) genes encode plant specific peptides exerting indispensable functions in a multitude of these developmental processes. Previously, we have described a CLE40 signaling module that regulates stemness in the distal root meristem (DRM). Here, we show that CLE40 is additionally needed to maintain the proximal root meristem (PRM). We demonstrate that in cle40 mutants, meristematic cells differentiate prematurely, resulting in shortened PRMs and ultimately, reduced root growth. Furthermore, we link these effects to increased cytokinin signaling that can be circumvented by preventing the perception of cytokinin. We highlight how increased cytokinin signaling leads to a change in auxin distribution mediated by SHORT HYPOCOTYL 2 (SHY2), which is ectopically activated if CLE40 is not active. Finally, we propose that the receptor BARELY ANY MERISTEM 1 (BAM1), but not its homolog BAM2, perceives CLE40 in the PRM.

developmental biology↗

bioRxiv2023

Climate, host and geography shape insect and fungal communities of trees

Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance suggesting that human-mediated transport may facilitate the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

ecology↗

bioRxiv2022

WiChR, a highly potassium selective channelrhodopsin for low-light two-photon neuronal inhibition

The electric excitability of muscle, heart and brain tissue relies on the precise interplay of Na+- and K+-selective ion channels. The involved ion fluxes are controlled in optogenetic studies using light-gated channelrhodopsins (ChRs). While non-selective cation-conducting ChRs are well-established for excitation, K+-selective ChRs (KCRs) for efficient inhibition have only recently come into reach. Here, we report the molecular analysis of recently discovered KCRs from the stramenopile Hyphochytrium catenoides and identify a novel type of hydrophobic K+-selectivity filter. Next, we demonstrate that the KCR signature motif is conserved in related stramenopile ChRs. Among them, WiChR from Wobblia lunata features an unmatched 80-fold preference for K+ over Na+, stable photocurrents under continuous illumination and a prolonged open state lifetime. Well expressed in neurons, WiChR allows two-photon inhibition at low irradiance and reduced tissue heating,_recommending WiChR as the long-awaited efficient and versatile optogenetic inhibitor.

neuroscience↗

bioRxiv2019

Structural basis for recognition of RALF peptides by LRX proteins during pollen tube growth

Plant reproduction relies on the highly regulated growth of the pollen tube for proper sperm delivery. This process is controlled by secreted RALF signaling peptides, which have been previously shown to be perceived by CrRLK1Ls membrane receptor-kinases and leucine-rich (LRR) extensin proteins (LRXs). Here we demonstrate that RALF peptides are active as folded, disulfide bond-stabilized proteins, which can bind to the LRR domain of LRX proteins with nanomolar affinity. Crystal structures of the LRX-RALF signaling complexes reveal LRX proteins as constitutive dimers. The N-terminal LRR domain containing the RALF binding site is tightly linked to the extensin domain via a cysteine-rich tail. Our biochemical and structural work reveals a complex signaling network by which RALF ligands may instruct different signaling proteins - here CrRLK1Ls and LRXs - through structurally different binding modes to orchestrate cell wall remodeling in rapidly growing pollen tubes.\n\nSignificancePlant reproduction relies on proper pollen tube growth to reach the female tissue and release the sperm cells. This process is highly regulated by a family of secreted signaling peptides that are recognized by cell-wall monitoring proteins to enable plant fertilization. Here, we report the crystal structure of the LRX-RALF cell-wall complex and we demonstrate that RALF peptides are active as folded proteins. RALFs are autocrine signaling proteins able to instruct LRX cell-wall modules and CrRKL1L receptors, through structurally different binding modes to coordinate pollen tube integrity.

plant biology↗

bioRxiv2018

Crystal structures of two tandem malectin-like receptor kinases involved in plant reproduction

A complex cell-to-cell communication between the male pollen tube and the female reproductive organs is required for plant fertilization. A family of Catharanthus roseus Receptor Kinase-1 ( CrRLK1L) membrane receptors has been genetically implicated in this process. Here we present crystal structures of the CrRLK1Ls ANXUR1 and 2 at 1.48 and 1.1 [A] resolution, respectively. Our structures reveal a novel arrangement of two malectin-like domains connected by a short {beta}hairpin linker and stabilized by calcium ions. The canonical carbohydrate interaction surfaces of related animal and bacterial carbohydrate binding modules are not conserved among plant CrRLK1Ls. In line with this, we failed to detect binding of chemically diverse oligosaccharides to ANXUR1 and HERCULES1. Instead, CrRLK1Ls have evolved a protein-protein interface between their malectin domains, which forms a deep cleft lined by highly conserved aromatic and polar residues. Analysis of the glycosylation pattern of different CrRLK1Ls and their oligomeric states together suggests that this cleft could resemble a binding site for a ligand required for CrRLK1Ls receptor activation.

plant biology↗

bioRxiv2018

Integration of Brassinosteroid and Phytosulfokine Signalling Controls Vascular Cell Fate in the Arabidopsis Root

Multicellularity arose independently in plants and animals, but invariably requires robust determination and maintenance of cell fate. This is exemplified by the highly specialized water-and nutrient-conducting cells of the plant vasculature, which are specified long before their commitment to terminal differentiation. Here, we show that the hormone receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is required for root vascular cell fate maintenance, as BRI1 mutants show ectopic xylem in procambial position. However, this phenotype is unrelated to classical brassinosteroid signalling outputs. Instead, BRI1 is required for the expression and function of its interaction partner RECEPTOR-LIKE PROTEIN 44 (RLP44), which, in turn, associates with the receptor for the peptide hormone phytosulfokine (PSK). We show that PSK signalling is required for the maintenance of procambial cell identity and is quantitatively controlled by RLP44, which promotes complex formation between the receptor for PSK and its co-receptor. Mimicking the loss of RLP44, PSK-related mutants show ectopic xylem in the position of procambium, whereas rlp44 can be rescued by exogenous PSK. Based on these findings, we propose that RLP44 controls cell fate by connecting BRI1 and PSK signalling, providing a mechanistic framework for the integration of signalling mediated by the plethora of plant receptor-like kinases at the plasma membrane.

plant biology↗

bioRxiv2018

A Comprehensive Tool Set for Inducible, Cell Type-Specific Gene Expression in Arabidopsis

Understanding the context-specific role of gene function is a key objective of modern biology. To this end, we generated a resource for inducible cell-type specific trans-activation based on the well-established combination of the chimeric GR-LhG4 transcription factor and the synthetic pOp promoter. Harnessing the flexibility of the GreenGate cloning system, we produced a comprehensive set of GR-LhG4 driver lines targeting most tissues in the Arabidopsis shoot and root with a strong focus on the indeterminate meristems. We show that, when combined with effectors under control of the pOp promoter, tight temporal and spatial control of gene expression is achieved. In particular, inducible expression in F1 plants obtained from crosses of driver and effector lines allows rapid assessment of the cell type-specific impact of an effector with high temporal resolution. Thus, our comprehensive and flexible toolbox is suited to overcome the limitations of ubiquitous genetic approaches, the outputs of which are often difficult to interpret due to widespread existence of compensatory mechanisms and the integration of diverging effects in different cell types.\n\nOne sentence summary: A set of lines enabling spatio-temporal control of gene expression in Arabidopsis.

plant biology↗