Goldstein B, Griego R, Wofsy C
Biophys J. 1984 Nov;46(5):573-86. doi: 10.1016/S0006-3495(84)84056-4.
A variety of receptors are known to aggregate in specialized cell surface structures called coated pits, prior to being internalized when the coated pits close off. At 37 degrees C on human fibroblasts, as well as on other cell types, a recycling process maintains a constant number of coated pits on the cell surface. In this paper, we explore implications for receptor aggregation and internalization of the two types of recycling models that have been proposed for the maintenance of the coated pit concentration. In one model, coated pits alternate between accessible and inaccessible states at fixed locations on the cell surface, while in the other model, coated pits recycle to random locations on the cell surface. We consider receptors that are randomly inserted in the membrane, move by pure diffusion with diffusion coefficient D, and are instantly and irreversibly trapped when they reach a coated pit boundary (the diffusion limit). For such receptors, we calculate for each of the two models: the mean time tau to reach a coated pit, the forward rate constant k+ for the interaction of a receptor with a coated pit, and the fraction phi of receptors aggregated in coated pits. We show that for the parameters that characterize coated pits on human fibroblasts, the way in which coated pits return to the surface has a negligible effect on the values of tau, k+, and phi for mobile receptors, D greater than or equal to 1.0 X 10(-11) cm2/s, but has a substantial effect for "immobile" receptors, D much less than 1 X 10(-11) cm2/s. We present numerical examples to show that it may be possible to distinguish between these models if one can monitor slowly diffusing receptors (D less than 1 X 10(-11) cm2/s) on cells whose coated pits have relatively short lifetimes (less than or equal to 1 min). Finally, we show that for the low-density lipoprotein (LDL) receptor on human fibroblasts (D = 4.5 X 10(-11) cm2/s), the predicted and observed values of K+ and phi are in close agreement. Therefore, even for slowly diffusing LDL receptor, unaided diffusion as the transport mechanism of receptors to coated pits is consistent with measured rates of LDL internalization.
已知多种受体在被称为被膜小窝的特殊细胞表面结构中聚集，之后当被膜小窝封闭时这些受体被内化。在37摄氏度下，对于人类成纤维细胞以及其他细胞类型，一个循环过程维持着细胞表面被膜小窝数量的恒定。在本文中，我们探讨了为维持被膜小窝浓度而提出的两种循环模型对受体聚集和内化的影响。在一种模型中，被膜小窝在细胞表面固定位置的可及和不可及状态之间交替，而在另一种模型中，被膜小窝循环到细胞表面的随机位置。我们考虑随机插入膜中、以扩散系数D进行纯扩散且当到达被膜小窝边界（扩散极限）时立即且不可逆地被捕获的受体。对于此类受体，我们针对两种模型分别计算：到达被膜小窝的平均时间τ、受体与被膜小窝相互作用的正向速率常数k + 以及聚集在被膜小窝中的受体比例φ。我们表明，对于表征人类成纤维细胞上被膜小窝的参数，被膜小窝回到表面的方式对移动受体（D大于或等于1.0×10⁻¹¹ cm²/s）的τ、k + 和φ值影响可忽略不计，但对“不移动”受体（D远小于1×10⁻¹¹ cm²/s）有显著影响。我们给出数值示例表明，如果能够监测被膜小窝寿命相对较短（小于或等于1分钟）的细胞上缓慢扩散的受体（D小于1×10⁻¹¹ cm²/s），则有可能区分这些模型。最后，我们表明对于人类成纤维细胞上的低密度脂蛋白（LDL）受体（D = 4.5×10⁻¹¹ cm²/s），k + 和φ的预测值与观测值密切一致。因此，即使对于缓慢扩散的LDL受体，受体通过自由扩散作为向被膜小窝的转运机制与测量的LDL内化速率是一致的。
