The lectin LecA sensitizes the human stretch-activated channel TREK-1 but not Piezo1 and binds selectively to cardiac non-myocytes

Abstract

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research was supported by the European Research Council (Advanced Grant CardioNECT, Project ID: #323099, PK) and a research grant from the Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin, #3091311631). Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). SAC are activated by stretch and changes in membrane curvature but their precise role in the heart is unclear. The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for bacterial cell invasion by inducing membrane curvature. We investigate whether LecA modulates SAC activity, namely TREK-1 and Piezo1 in human embryonic kidney (HEK) cells. Confocal microscopy and electron tomography were used to follow binding dynamics of LecA, and the ion channel activity was recorded using the patch-clamp technique. Additionally, freshly isolated cardiac cells were used for studies into cell type dependency of LecA binding. LecA binds within seconds to cell surface. Local plasma membrane invaginations are detected by 17 min of LecA exposure. LecA sensitizes TREK-1, but not Piezo1, to voltage and mechanical stimulation. In freshly isolated cardiac cells, LecA binds to non-myocytes, but not to cardiomyocytes from mouse, rabbit, pig, and human. Our results suggest that LecA may serve as a pharmacological tool to study cardiac SAC in a cell type-preferential manner. Abstract Figure. Graphical abstract