Hutchinson Andrew T, Ramsland Paul A, Jones Darren R, Agostino Mark, Lund Maria E, Jennings Cameron V, Bockhorni Vanessa, Yuriev Elizabeth, Edmundson Allen B, Raison Robert L
Department of Medical and Molecular Biosciences, University of Technology Sydney, Ultimo, New South Wales, Australia.
J Immunol. 2010 Oct 1;185(7):4179-88. doi: 10.4049/jimmunol.1001956. Epub 2010 Sep 3.
Free κ L chains (FκLCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which FκLCs interact with membranes remains unresolved. In this study, we show that FκLCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound FκLCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of FκLCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated FκLCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms.
游离κ轻链（FκLCs）在骨髓瘤细胞表面表达，正被评估为治疗多发性骨髓瘤的一个治疗靶点。尽管其具有临床潜力，但FκLCs与膜相互作用的机制仍未得到解决。在本研究中，我们表明FκLCs与骨髓瘤细胞质膜上的鞘磷脂相关联。此外，膜结合的FκLCs发生聚集，这表明聚集是其插入膜所必需的。最后，我们提出了一个模型，其中FκLCs与分泌囊泡膜上的鞘磷脂的结合通过自我聚集得以稳定，聚集的FκLCs在胞吐作用后暴露于质膜上。尽管众所周知蛋白质聚集体能结合膜，但这只是在细胞表面发现聚集体的第二个例子，而且该细胞还以天然形式分泌这种蛋白质。我们推测，许多其他易于聚集的蛋白质可能通过类似机制与细胞膜相关联。
