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Updated: Sep 4, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
Intra-cluster receptor density (IRD): A molecular switch for TNFR1 clusters' signaling
Subhamoy Jana1, Priyanka Roy1, Jibitesh Das2
1School of Biological Sciences, Indian Association for the Cultivation of Science; Kolkata 700032, India.
Abstract:
Tumor necrosis factor receptor 1 (TNFR1) signaling regulates cell fate in inflammation, immune responses, and tumorigenesis. While TNF-α-mediated TNFR1 pathways are well known, the role of receptor clustering remains unclear. Utilizing homo-FRET using fluorescence anisotropy, we show that intra-cluster receptor density (IRD) governs TNFR1 signaling outcomes. Soluble TNF-α (sTNF-α) increases IRD at cluster cores but decreases it at rims via receptor reorganization. Reducing IRD through membrane tension, zafirlukast, actin depolymerization, or cholesterol depletion suppresses sTNF-α signaling, whereas increasing IRD by lowering membrane tension or exposing cells in a 3D gel-like microenvironment triggers ligand-independent activation. These findings reveal IRD as a key regulator of receptor signaling, with potential relevance across related receptor families and innovative strategies in modulating TNFR1 signaling.
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