Lipid rafts are important for the association of RANK and TRAF6
Lipid rafts are important for the association of RANK and TRAF6
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DOI：
10.1038/emm.2003.38
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发表时间：
2003-08-31
影响因子：
12.8
通讯作者：
Lee, ZH
中科院分区：
文献类型：
--
作者：
Ha, H;Kwak, HB;Lee, ZH
筏，胆固醇和鞘脂丰富的膜微区，已被证明在免疫细胞活化中发挥重要作用。最近，筏涉及的信号转导的TNF受体（TNFR）家族的成员。在这项研究中，我们提供的证据表明，筏微结构域在RANK（NF-κ B受体激活剂）信号转导中起着至关重要的作用。我们发现，大多数异位表达的RANK和内源性TRAF 2和TRAF 6的实质性部分中检测到的低密度筏级分。此外，RANKL刺激增加了TRAF 6与筏的结合。筏的破坏阻断了RANK配体对TRAF 6的转运，并阻碍了RANK与TRAF 6之间的相互作用。我们的观察结果表明，适当的RANK信号需要筏膜微区的功能。
Rafts, cholesterol- and sphingolipid-rich membrane microdomains, have been shown to play an important role in immune cell activation. More recently rafts were implicated in the signal transduction by members of the TNF receptor (TNFR) family. In this study, we provide evidences that the raft microdomain has a crucial role in RANK (receptor activator of NF-kappaB) signaling. We found that the majority of the ectopically expressed RANK and substantial portion of endogenous TRAF2 and TRAF6 were detected in the low-density raft fractions. In addition, TRAF6 association with rafts was increased by RANKL stimulation. The disruption of rafts blocked the TRAF6 translocation by RANK ligand and impeded the interaction between RANK and TRAF6. Our observations demonstrate that proper RANK signaling requires the function of raft membrane microdomains.