Disruption of membrane cholesterol organization impairs the activity of PIEZO1 channel clusters

• DOI: 10.1085/jgp.201912515
• Publication Date: 2020-06-24T20:39:36Z
• Authors: Pietro Ridone; Elvis Pandzic; Massimo Vassalli; Charles D. Cox; Alexander Macmillan; Philip A. Gottlieb; Boris Martinac
• Keywords: Piezo1; Filipin; Cell membrane

The human mechanosensitive ion channel PIEZO1 is gated by membrane tension and regulates essential biological processes such as vascular development erythrocyte volume homeostasis. Currently, little known about plasma localization organization. Using a PIEZO1-GFP fusion protein, we investigated whether cholesterol enrichment or depletion methyl-β-cyclodextrin (MBCD) disruption of organization dynasore affects PIEZO1-GFP’s response to mechanical force. Electrophysiological recordings in the cell-attached configuration revealed that MBCD caused rightward shift pressure–response curve, increased latency stimuli, markedly slowed inactivation. same effects were seen native N2A cells. STORM superresolution imaging that, at nanoscale, channels associate clusters sensitive manipulation. Both cluster distribution diffusion rates affected treatment with (5 mM). Supplementation polyunsaturated fatty acids appeared sensitize applied pressure. Together, our results indicate function directly dependent on composition lateral domains, which coordinate activity clustered channels.