Jade Dawson
Research Mentor: Pedro Lowenstein
Mentor Department: Neurosurgery, Medicine
Author(s): Daiana Perez Visnuk
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 36
Abstract
Piezo1, a mechanosensitive ion channel, has been implicated in the regulation of cancer cell physiology. In this study, we investigated the subcellular localization of Piezo1 in glioblastoma cells in response to glutamatergic signaling. Cells were cultured under control conditions or treated with glutamate, revealing a translocation of Piezo1 from the plasma membrane to the nuclear envelope upon glutamate exposure, as detected by immunofluorescence. To further dissect the involvement of ionotropic glutamate receptors in this process, cells were treated with agonists and antagonists targeting AMPA, kainate, and NMDA receptor subtypes. Non-competitive antagonists for AMPA (CP-465022 hydrochloride) and a competitive antagonist of AMPA and kainate receptors (NBQX) demonstrated distinct patterns of Piezo1 distribution between the nucleus and cytoplasm, with NBQX exhibiting time-dependent effects. NMDA receptor modulation produced nuanced changes; antagonists including APV (a broad-spectrum NMDA receptor antagonist), TCN-201 (a GluN2A-selective NMDA receptor antagonist), and cerestat (a broad-spectrum NMDA receptor antagonist), as well as the agonist ((RS)-(tetrazol-5-yl) glycine), influenced Piezo1 localization diversely across compartments and time points. Notably, treatment with NMDA antagonists resulted in increased cytoplasmic localization, while NMDA agonist administration favored nuclear translocation. These findings suggest that glutamate-induced Piezo1 trafficking is mediated by specific ionotropic glutamate receptor pathways, with both receptor subtype and duration of exposure determining channel localization. This work advances our understanding of Piezo1 regulation through glutamatergic mechanisms in glioblastoma cells and may inform future strategies targeting mechanosensitive ion channels in cancer therapy.
