Biology subjects

Hyka, L.

Publications and source records attributed to Hyka, L..

3 recordsLinked to original sources

bioRxiv2026

ADAM10 tailors extracellular vesicles for content transfer rather than signaling by contact

Etxtracellular vesicles (EVs) support cell-to-cell communication, both in physiological and pathological contexts and emerge as new biomarkers and potential therapeutics. Yet, despite EVs holding huge promises, our understanding of core mechanisms governing EV signaling remains significantly underdeveloped. Our previous work indicated that syndecans and their cytosolic adaptor syntenin control the biogenesis of a major subset of small EVs (sEVs). Here we show that syndecans control the accumulation of ADAM10 into sEVs. ADAM10 promotes the formation of sEVs enriched in cleaved receptors (reducing sEV corona), supports the sorting of proteins with intracellular functions, and tailors sEVs for the delivery of their internal content, e.g. syntenin, into the cytosol of recipient cells. Conversely, inhibition of ADAM10 favors the production of sEVs bearing full-length, signaling-competent receptors/ligands and enhances contact-dependent signaling. These findings uncover a protease-regulated switch that tailors sEV composition and signaling modality, providing important new mechanistic insights into the core molecular pathways supporting EV-mediated communication.

cell biology↗

bioRxiv2026

Measuring capture, internalization and cytosolic delivery of extracellular vesicle-embedded syntenin

Extracellular vesicles (EVs) mediate cell-to-cell communication and are considered potential drug delivery vehicles. Nevertheless, whether EV-embedded cargo can be efficiently delivered into the cytosol of recipient cells remains debated. Here, we investigated the fate of syntenin, a well-established internal cargo of small EVs (sEVs). Using quantitative assays, we show that [~]85% of internalized sEV-embedded syntenin can be delivered to the cytosol of recipient cells within short periods of time. Yet, even at low dose, we find that the internalization of sEVs carrying syntenin is rather inefficient ([~]0.03% of the administered dose). Moreover, we observe that the capture of sEVs by recipient cells is non-saturable over time and largely more efficient than their internalization. Finally, we identify the N-terminal domain of syntenin and the phosphorylation state of a Src-targeted tyrosine residue in this domain, as key determinants for its incorporation into sEVs that support cytosolic delivery. These findings challenge, current views in the field by indicating that sEV internalization may be a marginal process (on the contrary to capture) and that cytosolic delivery can be highly efficient. Moreover, our study identifies molecular determinants governing cytosolic delivery of sEV-embedded syntenin.

cell biology↗

bioRxiv2026

A syndecan-based genetic approach to coat the surface of small extracellular vesicles with Nanobodies

Small extracellular vesicles (sEVs) are promising vehicles for targeted therapeutic delivery, but strategies for their surface functionalization remain limited. Here, we present a reliable and simple genetic approach that enables customized modification of sEV surfaces and supports enhanced sEV uptake by recipient cells. This strategy is based on the fusion of targeting moieties to the C-terminal fragment of syndecan-1 (SDC1-CTF), a peptide naturally enriched in sEVs. Combining various analytical approaches including single-vesicle analysis, we establish that this strategy enables decoration of up to 20% of secreted sEVs with nanobodies (Nbs). In quantitative bioluminescence assays, using concentrated conditioned media, we demonstrate that sEV-coating with anti-EGFR Nb supports enhanced sEV uptake by EGFR-expressing cells. This new strategy thus offers a robust and modular solution for endowing sEV surfaces with defined targeting properties to support further sEV-based therapeutic applications.

cell biology↗