Biology subjects

Kux, J. M.

Publications and source records attributed to Kux, J. M..

2 recordsLinked to original sources

bioRxiv2026

Coupling lysosomal polarity and purinergic signaling regulates B cell activation

B cell activation is initiated by engagement of the B cell receptor (BCR) with immobilized antigens, which triggers changes in cell polarity promoting the establishment of an immune synapse that is further shaped by signals from the microenvironment. However, how cell polarity coordinates the sensing of extracellular cues to regulate B cell activation remains unclear. Here, we investigated the impact of adenosine triphosphate (ATP), a conventional danger signal related to inflammation, on B cell function. We found that ATP released by B cells, as well as exogenously added ATP, acts as a promoter of the extraction and presentation of immobilized antigens. Endogenous ATP was produced by mitochondria recruited at the immune synapse and locally released via Pannexin 1 channels to sustain purinergic signaling at the immune synapse. We identified P2RX4 trafficking to the plasma membrane through the Rab6a+ trans-Golgi network and VAMP7+/LAMP1+ lysosomes as a key step in this response. In addition, the local activation of P2RX4 at the immune synapse triggered a migratory switch from motile to sessile, suggesting that this receptor acts as a negative regulator of B cell migration. These findings reveal ATP as a local enhancer of B cell function, and an unexpected role of P2RX4 as a molecular switch for B cell activation.

immunology↗

bioRxiv2024

Shape dynamics and migration of branched cells on complex networks

Migrating cells often face microenvironmental constraints that force them to extend multiple, often highly dynamic, protrusions, that compete to choose the new direction. However, the analysis of how cells coordinate shape dynamics during this directional decision-making process has been restricted to single junctions. Here, we present a theoretical model and the corresponding experimental proof of concept using in vivo and in vitro live-cell microscopy and a neuronal network-based image analysis pipeline, to explore the shape and migration dynamics of highly bifurcated cells during spontaneous random migration. We found that macrophages and endothelial cells display different migration regimes in a hexagonal adhesive network, despite sharing a mesenchymal migratory strategy. Macrophages moved faster and presented larger changes in cell length in comparison to endothelial cells. The theoretical model describes the behavior of both cells during directional decision-making, and it reveals a trade-off between exploration for directional cues and long-range migration efficiency, showing the fine tune regulation of shape dynamics in complex geometries. TeaserHighly branched cells require precise control of their shape dynamics to ensure microenvironment exploration while keeping their motility.

biophysics↗