A bstractRafts, cholesterol-and sphingolipid-rich m em brane m icrodom ains, have been show n to play an important role in im m une cell activation. M ore recently rafts w ere im plicated in the signal transduction by m em bers of the TNF receptor (TNFR) fam ily. In this study, we provide evidences that the raft m icrodom ain has a crucial role in RANK (receptor activator of NF-κB) signaling. W e found that the m ajority of the ectopically expressed RANK and substantial portion of endogenous TRAF2 and TRAF6 w ere detected in the low -density raft fractions. In addition, TRAF6 association w ith rafts was increased by RANKL stim ulation. The disruption of rafts blocked the TRAF6 translocation by RANK ligand and im peded the interaction betw een RANK and TRAF6. O ur observations dem onstrate that proper RANK signaling requires the function of raft m em brane m icrodom ains.
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