Biology subjects

Boermel, M.

Publications and source records attributed to Boermel, M..

3 recordsLinked to original sources

bioRxiv2026

A dsRNA Virus Converts Early Endosomes into Stable Replication Organelles Through Maturation Arrest and Retrograde Transport

Infectious bursal disease virus (IBDV) and infectious pancreatic necrosis virus (IPNV) are major animal pathogens that impose a heavy burden on the poultry and aquaculture industries. Yet, major aspects of their unique replication program remain unknown. IBDV is unusual among double-stranded RNA viruses in that it replicates in association with host endosomes. We previously demonstrated this association to be orchestrated by the viral protein VP3 and the early endosomal lipid phosphatidylinositol 3-phosphate [PtdIns(3)P], suggesting an essential role for VP3 in forming birnaviruses specialized replication compartments. Here, combining high-resolution fluorescence and correlative light-electron microscopy with diverse molecular and biochemical analyses, we define how the IBDV protein VP3 targets and remodels host endosomes, and establish that endosome-associated replication is conserved in members of the Birnaviridae family. We show that IBDV VP3 targets early endosomes via the PtdIns(3)P effector Early Endosomal Antigen 1 (EEA1) to arrest their maturation and prompt their association with the Golgi complex via ESCPE-1-mediated retrograde transport. We further show that IPNV also exploits endosomal membranes for replication in a PtdIns(3)P dependent manner, although for this virus VP3 engages endosomes through an EEA1-independent mechanism yet to be determined. This work uncovers how birnaviruses exploit a single viral protein to orchestrate endosome remodeling and intracellular trafficking to establish specialized replication compartments while revealing both conserved and host-adapted features of birnaviruses replication.

cell biology↗

bioRxiv2024

Cell volume regulates terminal differentiation of cultured human epidermal keratinocytes

Differentiation of cultured human epidermal stem cells is regulated by interactions with the underlying substrate. Whereas differentiation is typically stimulated when keratinocytes are prevented from spreading, we previously identified two micron-scale topographical substrates that regulate differentiation of spread cells. On one substrate (S1), individual cells interact with small circular topographies, and differentiation is stimulated; on the other (S2), cells interact with larger triangular topographies, and differentiation is inhibited. By scanning electron microscopy we visualised substrate interactions at higher resolution than previously and using live cell imaging we established that induction of the differentiation marker involucrin did not involve transient cell rounding on S1. Bulk gene expression profiling did not reveal any differences between cells on S1 and S2 prior to the selective upregulation of differentiation markers at 12h on S1 and cell stiffness was lower on both S1 and S2 than on flat substrates. Nevertheless, cells on S2 differed from cells on flat and S1 substrates because they exhibited reduced cell volume, prompting us to explore whether cell volume could regulate differentiation independent of culture substrate. Treatment with polyethylene glycol (PEG) reduced cell volume and inhibited differentiation regardless of whether keratinocytes were seeded on flat, S1 or S2 substrates, micropatterned islands or in suspension. Conversely, treatment with deionised water increased cell volume and stimulated differentiation of substrate adherent keratinocytes. On flat substrates treatment with the Ca2+ chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester or an inhibitor of the water channel aquaporin 3 blocked induction of differentiaton by deionised water, whereas the gadolinium3+, a stretch-activated calcium channel blocker, did not. Our studies identify a new mechanism by which keratinocyte-niche interactions regulate initiation of differentiation.

cell biology↗

bioRxiv2019

Cell surface mechanics gate stem cell differentiation

Cell differentiation typically occurs with concomitant shape transitions to enable specialized functions. To adopt a different shape, cells need to change the mechanical properties of their surface. However, whether conversely cell surface mechanics control the process of differentiation has been relatively unexplored. Here, we show that membrane mechanics gate the exit from naive pluripotency of mouse embryonic stem cells. By measuring membrane tension during differentiation, we find that naive stem cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. By mechanically tethering the plasma membrane to the cortex with a synthetic signalling-inert linker, we demonstrate that preventing this detachment forces stem cells to retain their naive pluripotent state. We thus identify a decrease in membrane-to-cortex attachment as a new cell-intrinsic mechanism that is essential for stem cells to exit pluripotency.

biophysics↗