Biology subjects

Carvalho, A. S.

Publications and source records attributed to Carvalho, A. S..

3 recordsLinked to original sources

bioRxiv2026

A Meta-Analysis of 515 Human Proteomes Defines the Core Composition and Contaminants of Plasma Extracellular Vesicles isolates

Plasma extracellular vesicles (EVs) are promising liquid biopsy biomarkers, yet their proteomic profiling remains confounded by co-isolated lipoproteins and soluble complexes. Here, we resolve this heterogeneity through a meta-analysis of 515 human plasma EV proteomes. We demonstrate that the reproducible core proteome is dominated by soluble host-response modules rather than unique vesicular markers. Deconvolution analysis resolved the isolate into distinct biological sources, distinguishing the hepatic secretome and immune complexes from vesicular signals. Crucially, canonical tetraspanins (CD9, ADAM10) clustered with platelet and erythrocyte proteins, indicating that the bulk tetraspanin signal derives from hematopoietic ectosome shedding. In contrast, ESCRT machinery (TSG101, ALIX) formed a distinct, lower-abundance cluster, physically separating endosomal biogenesis from membrane shedding. We provide a modular atlas that mathematically distinguishes the functional matrix of coisolates from vesicular cargo, establishing a new framework for interpreting biological origin in plasma EV proteomics.

systems biology↗

bioRxiv2021

LAMP2A regulates the loading of proteins into exosomes.

Exosomes are extracellular vesicles of endosomal origin released by virtually all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs and proteins between different cells, tissues or organs. However, the mechanisms that regulate the selective loading of cytosolic proteins into these vesicles are still largely unknow. Here we describe a mechanism whereby proteins containing a pentapeptide sequence, biochemically related to the KFERQ-motif, are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, this mechanism is independent of the ESCRT machinery components TSG101 and VPS4b and dependent on HSC70, CD63, Alix, Syntenin-1, Rab31 and ceramides. The transcription factor and master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. Additionally, by tagging fluorescent proteins with KFERQ-like sequences we were able to follow inter-organ transfer of exosomes in zebrafish larvae. Our findings identify LAMP2A as a key component in exosome biogenesis while opening new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.

cell biology↗

bioRxiv2021

Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait

Extracellular vesicles (EVs) mediate communication in physiological and pathological conditions. In the pathogenesis of type 2 diabetes, inter-organ communication plays an important role in its progress and metabolic surgery leads to its remission. Moreover, gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how gut senses metabolic alterations and whether this is transmitted to other tissues via EVs. Using a diet induced-prediabetic mouse model, we observed that protein packaging in gut derived EVs (GDE), specifically small intestine, is increased in prediabetes. Proteins related to lipid metabolism and to oxidative stress management were more abundant in prediabetic GDE compared to healthy controls. On the other hand, proteins related to glycolytic activity, as well as those responsible for the degradation of polyubiquitinated composites, were depleted in prediabetic GDE. Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis. Thus, suggesting that prediabetic alterations in small intestine are translated into modified GDE proteome, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues. This study highlights the importance of the small intestine as a tissue that propagates prediabetic metabolic dysfunction throughout the body and the importance of GDE as the messenger.

pathology↗