Biology subjects

Gaertner, K.

Publications and source records attributed to Gaertner, K..

5 recordsLinked to original sources

bioRxiv2026

Nutrient-responsive midgut turnover is spatially controlled by serotonin signaling

Barrier epithelia undergo rapid turnover, yet how spatial tissue heterogeneity and environmental cues shape turnover rates remains poorly understood. Here, we show that serotonin signaling spatially regulates homeostatic turnover of the Drosophila midgut epithelium in a nutrient-responsive manner. Organ-wide analysis revealed regions of constitutively high and low turnover, as well as areas whose renewal depends on nutrient intake. In rapidly renewing posterior regions, serotonin accumulates in enterocytes undergoing programmed cell death (erebosis) in response to nutrient availability. Serotonin signals through the conserved 5HT7 receptor to promote enteroblast (EB) maturation and migration-associated morphological changes. 5HT7 signaling is both necessary and sufficient for renewal in high-turnover regions, and its sustained disruption leads to epithelial multilayering. Mechanistically, 5HT7 signaling regulates genes involved in metabolic pathways, such as the serine biosynthesis pathway, and in the actin cytoskeleton, which drive EB maturation and morphological change, respectively. Together, our findings establish a signaling mechanism that links nutritional cues to the spatial regulation of barrier epithelium turnover.

physiology↗

bioRxiv2024

Exploring mitonuclear interactions in the regulation of cell physiology: insights from interspecies cybrids

Brown hares (Lepus europaeus) and mountain hares (Lepus timidus) frequently hybridize in regions where their range overlaps, producing fertile offspring and enabling gene flow between the species. Despite this, no hybrid species has emerged, suggesting that hybrid backcrosses may incur fitness costs. One potential mechanism for such costs involves the interactions between mitochondrial and nuclear gene products, where incompatibilities between species-specific alleles may reinforce species barriers and lead to hybrid breakdown. However, direct experimental evidence for this hypothesis remains limited. In this study, we used fibroblasts derived from skin biopsies of wild-caught hares to generate cytoplasmic hybrid (cybrid) cell lines, wherein mitochondria and mtDNA from one species were transferred to mitochondria-depleted cells of the other species, creating novel mitonuclear gene combinations while preserving the original diploid nuclear background. Employing a range of techniques - including transcriptomics, metabolomics, microscopy, and respirometry - we explored the consequences of mitochondrial transfer between these hare species. Our results reveal that in the studied species mitonuclear incompatibilities exhibit strong effects on cellular fitness but are limited to specific genotypes. We propose mechanisms of cellular-level incompatibility and their potential consequences for interspecific hybrids, offering new insights into the complexity of mitonuclear interactions.

cell biology↗

bioRxiv2024

The nuclear speckles protein SRRM2 is a new therapeutic target molecule on the surface of cancer cells

The membrane composition of extracellular vesicles (EVs) largely reflects that of the plasma membrane of the cell of origin. We therefore hypothesized that EVs are a source for the detection of hitherto unknown tumor-associated druggable target molecules. For this, we used EVs derived from cancer cell lines for an immunization of a rat. From this immunization, we obtained a monoclonal antibody specific for SRRM2, a protein involved in splicing a major component of nuclear speckles. Here, we used this antibody to demonstrate that SRRM2 is exposed at the surface of most cancer cell lines from various entities and, even more important, on cancer cells in vivo. Moreover, we demonstrate that SRRM2-specific CAR-T cells are killing SRRM2-positive cancer cells electively. Collectively, we identified SRRM2 as a promising new target molecule exposed on the cancer cell surface and show that our SRRM2-specific antibody can be used as a basis for the development of new targeted cancer therapies.

cancer biology↗

bioRxiv2024

A species difference in glycerol-3-phosphate metabolism reveals metabolic adaptations in hares

The temperate climate adapted brown hare (Lepus europaeus) and the cold-adapted mountain hare (Lepus timidus) are evolutionarily closely related and interfertile. Still, their cultured skin fibroblasts show clear differences in the expression of genes related to basic cellular metabolism. To study this further, we utilized targeted metabolomics analysis, metabolite tracing, and high-resolution respirometry, and identified significant differences in metabolic pathways associated with adaptive thermogenesis, including a higher rate of glycerol 3-phosphate (G3P) production in the mountain hare. We therefore investigated mitochondrial heat production and its dependence on G3P in the two hare species. The mountain hare maintained lower mitochondrial temperature and had weaker thermal change following OXPHOS inhibition. Manipulating mitochondrial glycerol 3-phosphate dehydrogenase (GPD2) levels demonstrated its role in mitochondrial thermogenesis and revealed species-specific function in maintaining mitochondrial membrane potential. This study unveils previously undocumented and unexpected species differences in the mitochondrial properties of fibroblasts that could indicate differences in metabolic adaptability. These findings also demonstrate the utility of cell culture models in assessing trait differences between species and their evolutionary significance, contributing to a deeper understanding of metabolic adaptation in animals and underscoring the potential of in vitro approaches for eco-physiological studies.

molecular biology↗

bioRxiv2020

Micro RNAs are minor constituents of extracellular vesicles and are hardly delivered to target cells

Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells transcriptome. The extent to which miRNAs are exported via the EV route and whether they contribute to cell-cell communication are controversial. To address these issues, we analyzed the capacity of EVs to deliver packaged miRNAs into target cells and to exert biological functions. We applied well-defined approaches to produce and characterize purified EVs with or without specific viral miRNAs. We found that only a small fraction of EVs carried miRNAs. EVs readily bound to different target cell types, but there was no EV-cell membrane fusion or delivery of cargo. Importantly, the functionality of cells exposed to miRNA-carrying EVs was not affected. These results suggest EV-borne miRNAs do not act as effectors and question their relevancy in paracrine cell-to-cell communication. AUTHOR SUMMARYThe majority of metazoan cells release vesicles of different types and origins, such as exosomes and microvesicles, now collectively termed extracellular vesicles (EVs). EVs have gained much attention because they contain microRNAs (miRNAs) and thus could regulate their specific mRNA targets in recipient or acceptor cells that take up EVs. Using a novel fusion assay with superior sensitivity and specificity, we revisited this claim but found no convincing evidence for an efficient functional uptake of EVs in many different cell lines and primary human blood cells. Even EVs engineered to fuse and deliver their miRNA cargo to recipient cells had no measurable effect on target mRNAs in very carefully controlled, quantitative experiments. Our negative results clearly indicate that EVs do not act as vehicles for miRNA-based cell-to-cell communication.

cell biology↗