Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel.
Biophys J. 2013 Aug 6;105(3):565-9. doi: 10.1016/j.bpj.2013.04.025.
Molecular exchange between the cell nucleus and cytoplasm is one of the most fundamental features of eukaryotic cell biology. The nuclear pores act as a conduit of this transport, both for cargo that crosses the pore autonomously as well as that whose translocation requires an intermediary receptor. The major class of such receptors is regulated by the small GTPase Ran, via whose interaction the nucleo-cytoplasmic transport system functions as a selective molecular pump. We propose a simple analytical model for transport that includes both translocation and receptor binding kinetics. The model is suitable for steady-state kinetics such as fluorescence recovery after photobleaching. Time constants appear as a combination of parameters whose effects on measured kinetics are not separable. Competitive cargo binding to receptors and large cytoplasmic volume buffer the transport properties of any particular cargo. Specific limits to the solutions provide a qualitative insight and interpretation of nuclear transport in the cellular context. Most significantly, we find that under realistic conditions receptor binding, rather than permeability of the nuclear pores, may be rate-limiting for nucleo-cytoplasmic exchange.
核质间的分子交换是真核细胞生物学的最基本特征之一。核孔作为这种运输的通道，对于自主穿过核孔的货物以及需要中间受体的易位货物都是如此。这类受体的主要类别受小分子 GTP 酶 Ran 调节，通过这种相互作用，核质转运系统作为一种选择性的分子泵发挥作用。我们提出了一种简单的分析模型，该模型包括易位和受体结合动力学。该模型适用于稳态动力学，例如光漂白后荧光恢复。时间常数表现为参数的组合，其对测量动力学的影响不可分离。与受体的竞争性货物结合和大的细胞质体积缓冲了任何特定货物的运输特性。特定解的限制提供了对细胞环境中核运输的定性洞察和解释。最重要的是，我们发现，在现实条件下，受体结合而不是核孔的通透性可能是核质交换的限速步骤。
