Recruitment of TNF ligands to lipid rafts is mediated by their physical association with caveolin‐1

• Published in: FEBS letters Vol. 596; no. 2; pp. 211 - 218
• Main Authors: Glukhova, Xenia A., Trizna, Julia A., Melnik, Bogdan S., Proussakova, Olga V., Beletsky, Igor P.
• Format: Journal Article
• Language: English
• Published: England 01.01.2022
• Subjects: Caveolin 1 - genetics; Caveolin 1 - metabolism; caveolin‐1; CD40 Ligand - genetics; CD40 Ligand - metabolism; CD40L; HeLa Cells; Humans; Ligands; lipid rafts; Membrane Microdomains - metabolism; physical association; Protein Binding; Protein Transport; TNF; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; CD40L; caveolin-1; lipid rafts; physical association; TNF
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.14257

Activities of the tumour necrosis factor (TNF) family members are associated with their targeting to lipid rafts, specialised regions of the plasma membrane. Herein, we investigated the physical association of TNF and its family members cluster of differentiation 40 ligand (CD40L) and tumour necrosis factor‐related apoptosis‐inducing ligand with caveolin‐1, a lipid raft resident protein. We discovered that the intracellular domains of TNF and CD40L interact with caveolin‐1, and the membrane proximal region of TNF is required for the binding of caveolin‐1 domains. Full‐length TNF can form a complex with caveolin‐1 in membrane rafts of HeLa cells, and caveolin‐1 knockdown leads to impaired TNF transport to rafts. These findings provide the first evidence of a direct interaction between TNF, CD40L and caveolin‐1 and suggest that caveolin‐1 may be responsible for recruiting TNF to lipid rafts. Effects of the TNF family ligands are associated with their targeting to lipid rafts. We found that TNF and its family member CD40L interact with caveolin‐1, a lipid raft resident protein, and caveolin‐1 knockdown leads to impaired TNF transport to rafts. This study reveals that the TNF–caveolin‐1 association may be responsible for recruiting TNF to lipid rafts.