Cytoplasmic exclusion as a basis for asymmetric nucleocytoplasmic solute distributions

Abstract

THE nuclear and cytoplasmic concentrations of solutes in cells are often unequal. This has been observed for ions^1,2, small molecules^3–5, and for macromolecules^6–10. The role of maintaining these concentration differentials is commonly assigned to the nuclear envelope, but this practice is predicated on a questionable analogy with the plasma membrane. Most of the information derived from tracer kinetics^4,8,9 and electrical resistance^10–13 indicates that the nuclear envelope is too permeable to distinguish or differentially transport small solutes. Thus, we must look to other, presumably equilibrium, mechanisms to account for many nucleocytoplasmic solute asymmetries. One useful step in the analysis of solute distributions between two phases is to establish a reference phase to which the concentrations of substances in the other two phases can be compared. A suitable reference phase for cytoplasm and nucleus cannot, of course, be separated from them by the cell membrane, which itself has complex, asymmetric transport properties. Thus, the reference phase must be intracellular. We have carried out experiments in which a defined aqueous reference phase (a gelatin gel) was introduced into the cytoplasm, and the partition of solutes between this phase, cytoplasm, and nucleus was determined. We deal here with the intracellular distribution of ³H-sucrose—a small, non-metabolised substance which reaches a greater concentration in the nucleus than in the cytoplasm⁴.