Biology subjects

Schjoldager, K. T.

Publications and source records attributed to Schjoldager, K. T..

5 recordsLinked to original sources

bioRxiv2026

Insights into Spontaneous Curvature in Complex Membranes from Dual-Tether Pulling Experiments

Spontaneous curvature characterizes the propensity of a membrane to bend in a specific direction. It is therefore crucial in the multitude of cellular processes that involve membrane shape remodelling. Yet, experimentally quantifying the spontaneous curvature remains a significant challenge in complex biological membranes, as their heterogeneity causes ambiguities in spontaneous curvatures physical interpretation. Here, we introduce a general experiment-simulation framework to measure an effective spontaneous curvature using dual-direction tether pulling from cell-attached giant plasma membrane vesicles (GPMVs) and mesoscale simulations. For homogeneous membranes, the force difference between inward and outward pulls yields a tension-independent readout of spontaneous curvature. We show that this continuum observable can be generalized to the mean of the spontaneous curvature in a heterogeneous membrane, independent of the underlying microscopic spontaneous curvature distribution. Applied to HEK-derived GPMVs, a baseline negative spontaneous curvature of the plasma membrane is revealed. Sucrose treatment and extracellular addition of Annexin A5 systematically shift the effective spontaneous curvature, while mucin reporter overexpression does not measurably alter it under the conditions tested. We also measure the curvature imprint of individual fluorescently tagged proteins through a sorting index. Benchmarked with Annexin A5, our scheme recovers curvature imprints very similar to previous atomistic molecular dynamics simulations. Taken together this makes spontaneous curvature accessible as a directly measurable material property of native membranes and membrane-proteins, enabling quantitative studies of membrane remodelling across diverse cellular processes.

biophysics↗

bioRxiv2026

Prey-specific toxins provide broad venom activity in cephalopods

Cephalopods are among the oceans most sophisticated predators that use camouflage, complex behaviors, and venom to subdue a wide range of prey. However, the functional role of venom across diverse prey remains poorly understood, particularly whether cephalopods deploy venom to capture fish. Through comprehensive transcriptomic profiling of venom glands, we identify toxins with molecular signatures of prey-specific adaptation, including a previously unrecognized family of peptide toxins, octotensins, that evolved through convergent evolution to mimic the vertebrate hormone neurotensin. Functional assays and cryo-electron microscopy demonstrate that octotensins potently activate fish and human neurotensin receptor 1, engage this target in a near-identical manner to the chordate hormone, and induce acute hypotension in rodents. Together, our findings demonstrate that cephalopods achieve broad venom activity through phylum-specific toxins, including those targeting fish, revealing an evolutionary strategy by which generalist predators can capture phylogenetically diverse prey. One-Sentence SummaryCephalopod venom comprises prey-specific toxins, including neurotensin-mimicking peptides that target fish.

systems biology↗

bioRxiv2026

Mimics of the chordate gut-brain hormone neurotensin in parasitic intestinal hookworms

Hookworms of the family Ancylostomatidae are intestinal parasites that infect hundreds of millions of people worldwide, contributing to malnutrition, anemia, and impaired development. While hookworms are known to secrete immunomodulatory molecules to evade host defenses, it has been unclear whether they also exploit host hormonal signaling. Here, we identify a previously unrecognized family of hookworm peptides, which we term ancylotensins. Ancylotensins share strong sequence similarity with the chordate hormone neurotensin, a key regulator of metabolism, gut-brain communication, and intestinal function. In vitro pharmacological assays, ex vivo gut contractility studies, and cryo-electron microscopy demonstrate that ancylotensins closely replicate both the structural and functional properties of mammalian neurotensin to modulate gut function. Furthermore, ancylotensins do not share common ancestry with chordate neurotensin and instead evolved independently via convergent evolution. These findings reveal the existence of gut peptide mimicry as a mechanism by which intestinal parasites can manipulate host physiology.

biochemistry↗

bioRxiv2025

Genetic and preclinical evidence implicating chondroitin sulfate as a matritherapeutic target for the treatment of type 2 diabetes

Peptide-based treatments for type 2 diabetes (T2D) are often limited by variable patient responses, frequent discontinuation, and substantial costs. Emerging lines of evidence link the extracellular matrix (ECM) to the pathophysiology of T2D, highlighting a largely unexplored modality for managing this heterogenous disease. Chondroitin sulfate (CS), a major glycosaminoglycan in the ECM, has been suggested to improve cardiometabolic health in preclinical research. However, the human genetic and pharmacological basis for CS as an anti-diabetic target is largely unexplored. Here, we uncover novel and robust links between 12 CS-related genes and both glycemic traits and the risk of T2D in hu-mans. Complementing this, administration of CS leads to a profound lowering of blood glucose levels in severely diabetic mice and improves glucose tolerance and cardiac clearance of circulating glucose in diet-induced obese mice without causing hypoglyce-mia or other adverse effects. The improvement in glycemic control is accompanied by increased glucose-stimulated insulin secretion and enhanced insulin action, effects which seem to occur independent of the incretin system. The combination of human genetic evidence and appealing pharmacodynamic features highlights CS as a promising ECM-target for developing novel pharmacotherapies that complement current treatments for T2D.

physiology↗

bioRxiv2024

Neuronal loss of Galnt2 Impairs O-glycosylation and Leads to Neurobehavioral Deficits Mimicking GALNT2-CDG

GALNT2-CDG is a multi-system genetic disorder due to biallelic pathogenic mutations in GALNT2, which encodes a ubiquitously expressed Golgi-localized glycosyltransferase that initiates mucin-type O-glycosylation. Affected individuals exhibit dysmorphic facial features, short stature, decreased HDL-C, and notable impairments in brain function. GALNT2-CDG patients show global developmental delay without speech development, childhood epilepsy, autistic-like features, and white-matter brain abnormalities. The extent of O-glycosylation in brain development and function remains poorly understood. To address this question, we selectively ablated Galnt2 from pan-neuronal cells in the brain and found that conditional knockout mice exhibit deficits across numerous behavioral domains, including locomotion, motor coordination, sociability, learning, and memory, as well as experience spontaneous seizures, recapitulating characteristic neurological manifestations of GALNT2-CDG. Given the catalytic activity of GALNT2 to initiate mucin-type O-glycosylation, we used glycoproteomics to identify disrupted O-glycosylation in synaptosomes purified from cortical tissues. We ascertained a non-redundant, isoform-specific contribution of GALNT2 to the cortical synaptosomal O-glycoproteome, identifying candidate glycoproteins and disrupted O-glycosites that accompany behavioral abnormalities in knockout mice. These findings demonstrate functional impact of O-glycosylation in neurons, implicating roles of O-glycosylation in diverse molecular and cellular pathways related to neuronal function and provide new opportunities to gain insights into the neurological pathophysiology of GALNT2-CDG.

neuroscience↗