Baier C J, Barrantes F J
UNESCO Chair of Biophysics and Molecular Neurobiology and Instituto de Investigaciones Bioquímicas de Bahía Blanca, Bahía Blanca, Argentina.
J Neurochem. 2007 May;101(4):1072-84. doi: 10.1111/j.1471-4159.2007.04561.x. Epub 2007 Apr 16.
The nicotinic acetylcholine receptor (AChR) is the prototype ligand-gated ion channel, and its function is dependent on its lipid environment. In order to study the involvement of sphingolipids (SL) in AChR trafficking, we used pharmacological approaches to dissect the SL biosynthetic pathway in CHO-K1/A5 cells heterologously expressing the muscle-type AChR. When SL biosynthesis was impaired, the cell surface targeting of AChR diminished with a concomitant increase in the intracellular receptor pool. The SL-inhibiting drugs increased unassembled AChR forms, which were retained at the endoplasmic reticulum (ER). These effects on AChR biogenesis and trafficking could be reversed by the addition of exogenous SL, such as sphingomyelin. On the basis of these effects we propose a 'chaperone-like' SL intervention at early stages of the AChR biosynthetic pathway, affecting both the efficiency of the assembly process and subsequent receptor trafficking to the cell surface.
烟碱型乙酰胆碱受体（AChR）是配体门控离子通道的原型，其功能依赖于脂质环境。为了研究鞘脂（SL）在AChR转运中的作用，我们采用药理学方法剖析了异源表达肌肉型AChR的CHO-K1/A5细胞中的SL生物合成途径。当SL生物合成受损时，AChR的细胞表面靶向作用减弱，同时细胞内受体池增加。抑制SL的药物增加了未组装的AChR形式，这些形式保留在内质网（ER）中。添加外源性SL（如鞘磷脂）可逆转这些对AChR生物发生和转运的影响。基于这些效应，我们提出在AChR生物合成途径的早期阶段存在一种“伴侣样”的SL干预，它影响组装过程的效率以及随后受体向细胞表面的转运。
