Biology subjects

Schmoranzer, J.

Publications and source records attributed to Schmoranzer, J..

10 recordsLinked to original sources

bioRxiv2025

A novel enteric pacemaker activity in Drosophila

Enteric organs such as the gut and stomach display the intrinsic ability to generate slow-wave potentials, rhythmic electrochemical events acting as key regulators of gastrointestinal motility. In mammals, slow waves occur as a result of the pacemaker activity of Interstitial Cells of Cajal (ICCs) which, by recruiting visceral muscles, ultimately lead to peristalsis. Here, we uncover and characterize a novel mechanism in Drosophila by which the midgut is able to generate strong muscular whip-like contractions. This pacemaker activity, here named superstalsis, is only active at certain physiological conditions and is selectively linked to longitudinal visceral muscle activation. Furthermore, we identify in Subdued, an ortholog gene of the ANO1/TMEM16A family, a marker for peristalsis in Drosophila, specifically associated with circular muscle activity. As fasting and bacterial infections cause specific changes in the intestinal motility profiles in vivo, we propose that the gut can autonomously alter the peristalsis/superstalsis balance to efficiently respond to diverse pathological and homeostatic events.

physiology↗

bioRxiv2025

Multiscale imaging of cytokinesis

After separation of duplicated genetic material, animal cells divide by cytokinesis. This process involves several simultaneous and successive steps of molecular reorganization at cell membrane, cortex and the spindle apparatus as the cleavage furrow ingresses and the spindle is transformed into the intercellular bridge. Dozens of proteins play a role in cytokinesis. However, a comprehensive view of their successive nanoscale reorganizations over cytokinesis remains untractable with current microscopy methods. Here, we developed a multimodal imaging and analysis framework to investigate the relative organization of key cytokinetic molecules over time. We extract cytokinetic hallmarks from live-cell lattice light-sheet and expansion microscopy (ExM) to computationally define pseudotime and align nanoscale ExM images of cytokinesis. We discover a cytokinetic substep and create nanoscale maps of the intercellular bridge and the midbody in 6 stages for 20 involved molecules. We thus provide a framework for nanoscale analysis of cytokinesis, a process fundamental to life.

cell biology↗

bioRxiv2025

Temporal dynamics of neuroplasticity and neurodegeneration in the central auditory system following noise-induced hearing loss: A multimodal imaging and histological study

Noise-induced hearing loss (NIHL) is a sensorineural disorder that triggers profound neuroplastic and neurodegenerative consequences in the central auditory nervous system (CNS). This study examined how neuronal density, axonal integrity and glutamatergic and GABAergic neurotransmission are affected after acute overstimulation in the central inferior colliculus (CIC) and the ventral medial geniculate body of the thalamus (MGV). To achieve this, a correlative multimodal approach combining audiometric, magnetic resonance imaging (MRI) and histological biomarkers was performed. Adult mice were noise-exposed to broadband white noise (5-20 kHz) for 3 hours at either high (115 dB SPL) or moderate (90 dB SPL) intensity, while unexposed mice were used as controls. Separate cohorts of mice were investigated 1-, 7-, 56- and 84-days post-exposure using in vivo magnetic resonance imaging (MRI) techniques: Voxel-based morphometry (VBM) of gray matter density (GMD), diffusion MRI (dMRI) of microstructure and connectivity, and single-voxel proton magnetic resonance spectroscopy (1H-MRS) for glutamate and GABA quantification. Frequency-specific auditory brainstem responses (ABR) were recorded at 4, 8, 16 and 32 kHz before and after exposure to examine hearing threshold (HT) shifts. Following imaging, brains were processed for fluorescence immunohistochemistry (FIHC) targeting Neuronal Nuclear Protein (NeuN), 4,6-diamidino-2-fenilindo (DAPI), Neurofilament (SMI312), vesicular GABA transporter (VGAT), and vesicular glutamate transporters 1 (VGLUT1) and 2 (VGLUT2). HTs were significantly elevated 7d, 56d and 84d after 115 dB noise exposure, suggesting a NIHL phenotype. Neurofilament density significantly increased in the CIC and MGV 1d after 115 dB noise exposure, and returned to baseline at later time points. dMRI transient microstructural alterations were observed 7d after 90 dB noise exposure. Glutamate and GABA decreases 84d after 90 dB exposure were also detected. Moreover, correlation analysis between audiometric, histological and MRI datasets revealed scarce relationships between the investigated parameters. These findings advance our understanding of the CNS adaptations of NIHL and emphasizes the need for more sensitive and integrative approaches to identify robust biomarkers of central auditory dysfunction.

neuroscience↗

bioRxiv2025

Nanoscale Mapping Reveals Periodic Organization of Neutrophil Extracellular Trap Proteins

Neutrophils are essential cells of the innate immune system that release Neutrophil Extracellular Traps (NETs) via NETosis. This specialized cell death pathway results in the extrusion of decondensed chromatin into the extracellular space. NET formation participates in antimicrobial defense and coagulation but dysregulated NETosis can contribute to neoplasticity, coagulopathy, and autoimmune disease. Here, we present a workflow combining optimized sample preparation, super-resolution imaging and quantitative bioimage analysis to investigate the nanoscale organization of NETs. Our newly developed analysis tool, NanoNET, facilitated the automated identification of DNA filaments and the analyses of NET binding proteins along those filaments through auto- and cross-correlation. We identify specific NET proteins, including neutrophil elastase (NE) and proteinase 3 (PR3), that are bound along DNA strands in a periodic fashion that mirrored nucleosomes. Cross-correlation of NE and PR3 with nucleosomes revealed that these proteins were highly colocalized suggesting that they dock onto or around nucleosomes. The presented workflow and analysis tools represent a significant methodological advance for studying protein distributions along NETs and along filamentous structures in general. Understanding how NET filaments are organized is a critical step toward elucidating both their formation and function.

cell biology↗

bioRxiv2024

Identification and characterization of a synaptic active zone assembly protein

At presynaptic active zones (AZs), scaffold proteins play a crucial role in coordinating synaptic vesicle (SV) release and forming intricate nanoarchitectures essential for synaptic function. Despite their suspected importance, factors governing the assembly of nanoscale AZ scaffolds have remained elusive. Here, we identify "Blobby" as a novel regulator of AZ nanopatterning, localized within the AZ scaffold. Genetic loss of the extended Blobby protein led to aberrant accumulation of AZ scaffold proteins ("blobs") and disrupted the nanoscale architecture of the AZ scaffold, resulting in a significant reduction in the packing density of voltage-gated Ca2+ channels at AZs, as observed through intravital single-molecule imaging. This disruption correlated with decreased evoked synaptic currents and SV release probability. Our findings suggest that Blobby plays a crucial role in switching the AZ scaffold into a state which allows to fine-tune the dynamic nanopatterning of Ca2+ channels to maintain proper release.

neuroscience↗

bioRxiv2024

Phosphorylation of PLPPR3 membrane proteins as signaling integrator at neuronal synapses

Phospholipid-phosphatase related protein 3 (PLPPR3, previously known as Plasticity Related Gene 2 or PRG2) belongs to a family of transmembrane proteins, highly expressed in neuronal development, which regulate critical growth processes in neurons. Prior work established crucial functions of PLPPR3 in axon guidance, filopodia formation and axon branching. However, little is known regarding the signaling events regulating PLPPR3 function. We identify here 26 high-confidence phosphorylation sites in the intracellular domain of PLPPR3 using mass spectrometry. Biochemical characterization established one of these - S351 - as a bona fide phosphorylation site of PKA. Experiments in neuronal cell lines suggest that phosphorylation of S351 does not regulate filopodia formation. Instead, it regulates binding to BASP1, a signaling molecule previously implicated in axonal growth and regeneration. Interestingly, both PLPPR3 intracellular domain and BASP1 enrich in presynapses in primary neurons. We propose that the presynaptic PLPPR3-BASP1 complex may function as novel signaling integrator at neuronal synapses.

neuroscience↗

bioRxiv2021

Simultaneous multicolor DNA-PAINT without sequential fluid exchange using spectral demixing

Several variants of multicolor single-molecule localization microscopy (SMLM) have been developed to resolve the spatial relationship of nanoscale structures in biological samples. The oligonucleotide-based SMLM approach DNA-PAINT robustly achieves nanometer localization precision and can be used to count binding sites within nanostructures. However, multicolor DNA-PAINT has primarily been realized by Exchange-PAINT that requires sequential exchange of the imaging solution and thus leads to extended acquisition times. To alleviate the need for fluid exchange and to speed up the acquisition of current multichannel DNA-PAINT, we here present a novel approach that combines DNA-PAINT with simultaneous multicolor acquisition using spectral demixing (SD). By using newly designed probes and a novel multichannel registration procedure we achieve simultaneous multicolor SD-DNA-PAINT with minimal crosstalk. We demonstrate high localization precision (3 - 6 nm) and multicolor registration of dual and triple-color SD-DNA-PAINT by resolving patterns on DNA origami nanostructures and cellular structures.

biophysics↗

bioRxiv2021

Incorporating structural knowledge into unsupervised deep learning for two-photon imaging data

Live imaging techniques, such as two-photon imaging, promise novel insights into cellular activity patterns at a high spatio-temporal resolution. While current deep learning approaches typically focus on specific supervised tasks in the analysis of such data, we investigate how structural knowledge can be incorporated into an unsupervised generative deep learning model directly at the level of the video frames. We exemplify the proposed approach with two-photon imaging data from hippocampal CA1 neurons in mice, where we account for spatial structure with convolutional neural network components, disentangle the neural activity of interest from the neuropil background signal with separate foreground and background encoders and model gradual temporal changes by imposing smoothness constraints. Taken together, our results illustrate how such architecture choices facilitate a modeling approach that combines the flexibility of deep learning with the benefits of domain knowledge, providing an interpretable, purely image-based model of activity signals from live imaging data. Teaser sentenceUsing a neural network architecture that reflects domain knowledge provides an interpretable model of live cell imaging data.

bioinformatics↗

bioRxiv2020

The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAA receptors at the periphery of excitatory synapses

Recent advances in imaging technology have highlighted that scaffold proteins and receptors are arranged in sub-synaptic nanodomains. The synaptic MAGUK scaffold protein MPP2 is a component of AMPA receptor-associated protein complexes and also binds to the synaptic cell adhesion molecule SynCAM1. Using super-resolution imaging, we now show that MPP2 and SynCAM1 are situated at the periphery of the postsynaptic density. In order to explore MPP2-associated protein complexes, we used a quantitative comparative mass spectrometry approach and identified multiple GABAA receptor subunits among the novel synaptic MPP2 interactors. We further show that GABAA receptors are found together with MPP2 in a subset of dendritic spines and thus highlight MPP2 as a scaffold molecule capable of acting as an adaptor molecule that links peripheral synaptic elements critical for inhibitory regulation to central structures at the PSD of glutamatergic synapses.

neuroscience↗

bioRxiv2019

DypFISH: Dynamic Patterned FISH to Interrogate RNA and Protein Spatial and Temporal Subcellular Distribution

Advances in single cell RNA sequencing have allowed for the identification and characterization of cellular subtypes based on quantification of the number of transcripts in each cell. However, cells may differ not only in the number of mRNA transcripts that they exhibit, but also in their spatial and temporal distribution, intrinsic to the definition of their cellular state. Here we describe DypFISH, an approach to quantitatively investigate the spatial and temporal subcellular localization of RNA and protein, by combining micropatterning of cells with fluorescence microscopy at high resolution. We introduce a range of analytical techniques for quantitatively interrogating single molecule RNA FISH data in combination with protein immunolabeling over time. Strikingly, our results show that constraining cellular architecture reduces variation in subcellular mRNA and protein distributions, allowing the characterization of their localization and dynamics with high reproducibility. Many tissues contain cells that exist in similar constrained architectures. Thus DypFISH reveals reproducible patterns of clustering, strong correlative influences of mRNA-protein localization on MTOC orientation when they are present and interdependent dynamics globally and at specific subcellular locations which can be extended to physiological systems.

systems biology↗