Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering
Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering
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DOI：
10.1523/jneurosci.2807-05.2006
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发表时间：
2006-05-03
影响因子：
5.3
通讯作者：
Mei, L
中科院分区：
文献类型：
--
作者：
Zhu, D;Xiong, WC;Mei, L
运动神经元衍生因子Agrin和肌肉特异性受体酪氨酸激酶（MuSK）对于在结后膜上聚集乙酰胆碱受体（AChR）是必不可少的。然而，潜在的信号机制仍然不明确。我们发现，agrin刺激AChR动态易位到质膜中的脂质筏-胆固醇和鞘脂丰富的微域。这需要MuSK分裂成脂筏并激活。脂筏的破坏抑制了MuSK的激活、下游信号传导和AChR聚集。Rapsyn是AChR聚集所必需的细胞内蛋白，它组成性地位于脂筏中，但当脂筏受到干扰时，它与AChR的相互作用被抑制。这些结果表明，脂筏可能通过促进agrin/MuSK信号传导以及受体与rapsyn之间的相互作用来调节AChR的聚集，这两者都是AChR聚集和维持所必需的。这些结果提供了对AChR簇形成机制的深入了解。
Agrin, a motoneuron-derived factor, and the muscle-specific receptor tyrosine kinase ( MuSK) are essential for the acetylcholine receptor ( AChR) clustering at the postjunctional membrane. However, the underlying signaling mechanisms remain poorly defined. We show that agrin stimulates a dynamic translocation of the AChR into lipid rafts-cholesterol and sphingolipid-rich microdomains in the plasma membrane. This follows MuSK partition into lipid rafts and requires its activation. Disruption of lipid rafts inhibits MuSK activation and downstream signaling and AChR clustering in response to agrin. Rapsyn, an intracellular protein necessary for AChR clustering, is located constitutively in lipid rafts, but its interaction with the AChR is inhibited when lipid rafts are perturbed. These results reveal that lipid rafts may regulate AChR clustering by facilitating the agrin/MuSK signaling and the interaction between the receptor and rapsyn, both necessary for AChR clustering and maintenance. These results provide insight into mechanisms of AChR cluster formation.