Biology subjects

Bartolome, A.

Publications and source records attributed to Bartolome, A..

5 recordsLinked to original sources

bioRxiv2026

Chemokine and opioid peptide scavenging through constitutive and ligand-induced release of ACKR3-bearing extracellular vesicles

Atypical chemokine receptors (ACKRs) are non-signaling GPCRs that regulate ligand availability, with ACKR3 functioning as a dual scavenger of chemokines and opioid peptides. Here, we demonstrate that following ligand stimulation, besides the canonical internalization, ACKR3 is released on extracellular vesicles (EVs). ACKR3 was also found on EVs released under basal conditions, although to a lesser extent. These observations were confirmed across multiple cellular contexts, including endogenous systems. Mechanistically, basal and ligand-induced EV release are independent of GRKs and {beta}-arrestin but each relies on distinct trafficking routes and C-terminal determinants. Ligand-induced EV release is associated with plasma membrane localization and receptor recycling pathways. In contrast, basal EV release is governed by intracellular sorting processes and influenced by receptor ubiquitination and RAMP3. Functionally, EV-associated ACKR3 retains high-affinity ligand binding, enabling sequestration of CXCL12 and opioid peptides and thereby attenuating their signaling through CXCR4 and MOR. We also show that the release on EVs, in particular under basal conditions, is observed for other receptors such as KOR, CXCR4 and several ACKRs. Collectively, these findings establish EVs as regulators in chemokine and opioid systems and as a previously underappreciated dimension of ACKR3 and more broadly GPCR biology.

Cell Biology↗

bioRxiv2026

Unveiling the Toxicological and Allelopathic Effects of Pteridium aquilinum: Chemical Profiling and Biological Assays

The fern Pteridium aquilinum (bracken) is among the world most widespread plants and poses serious ecological and health risks due to the presence of illudane glycosides (IGs), carcinogenic compounds that particularly affect grazing livestock. This study determined the presence of IGs in plant extracts and in water samples from the Asturias region (northern Spain), an area characterized by intensive cattle farming, and assessed the genotoxic potential, and allelopathic effects of these samples. The glycosides ptaquiloside (PTA) and ptesculentoside (PTE), together with the degradation products pterosin A and pterosin B, were quantified in in vitro-cultured gametophytes and young sporophytes, spring-collected croziers, and autumn water samples from several bracken-infested sites. All sampling locations contained IGs in both plant and water samples, with particularly high concentrations of PTA detected in croziers from Brana Vieja (Somiedo), where cattle deaths had been reported. In vivo genotoxicity assays, using Drosophila melanogaster, revealed induction of somatic mutations and recombination events by aqueous plant extracts and of somatic mutations by water samples. The genotoxic activity of plant extracts, but not that of water samples, was associated with pterosins A and B. Moreover, comet assays in cultured human cells confirmed the genotoxic activity of plant extracts. Unexpectedly, allelopathic bioassays indicated a possible phytostimulatory rather than inhibitory effect of bracken extracts on the germination of meadow species. These findings underscore the widespread presence and biological activity of bracken in northern Spain and highlight the urgent need for management strategies to mitigate the ecological and toxicological threats posed by bracken proliferation.

pharmacology and toxicology↗

bioRxiv2022

ProteasomeID: quantitative mapping of proteasome interactomes and substrates for in vitro and in vivo studies

Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite the relevance for human disease and drug development, no method currently exists to monitor proteasome composition and interactions in vivo in animal models. To fill this gap, we developed a strategy based on tagging of proteasomes with promiscuous biotin ligases and generated a new mouse model enabling the quantification of proteasome interactions by mass spectrometry. We show that biotin ligases can be incorporated in fully assembled proteasomes without negative impact on their activity. We demonstrate the utility of our method by identifying novel proteasome-interacting proteins, charting interactomes across mouse organs, and showing that proximity-labeling enables the identification of both endogenous and small molecule-induced proteasome substrates.

biochemistry↗

bioRxiv2020

Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other {gamma}-secretase ({gamma}S) targets, we hypothesized that ACE2 may be affected by {gamma}S proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by {gamma}S, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of {gamma}S results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of {gamma}S does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.

cell biology↗

bioRxiv2019

Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation

A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly / dis-assembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is the major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration. HighlightsO_LIProgressive loss of stoichiometry affects multiple protein complexes C_LIO_LIRibosomes aggregate in old brains C_LIO_LIPartial reduction of proteasome activity is sufficient to induce loss of stoichiometry C_LIO_LIReduced proteasome levels are a major risk factor for early death in killifish C_LI

systems biology↗