Import of proteins into the nucleus proceeds through nuclear pore complexes
and is largely mediated by nuclear transport receptors of the importin bet
a family that use direct RanGTP-binding to regulate the interaction with th
eir cargoes. We investigated nuclear import of the linker histone H1 and fo
und that two receptors, importin beta (Imp beta) and importin 7 (Imp7, RanB
P7), play a critical role in this process. Individually, the two import rec
eptors bind H1 weakly, but binding is strong for the Imp beta/Imp7 heterodi
mer. Consistent with this, import of H1 into nuclei of permeabilized mammal
ian cells requires exogenous Imp beta together with Imp7, Import by the Imp
7/Imp beta heterodimer is strictly Ran dependent, the Ran-requiring step mo
st likely being the disassembly of the cargo-receptor complex following tra
nslocation into the nucleus. Disassembly is brought about by direct binding
of RanGTP to Imp beta and Imp7, whereby the two Ran-binding sites act syne
rgistically, However, whereas an Imp beta/RanGTP interaction appears essent
ial for H1 import, Ran-binding to Imp7 is dispensable. Thus, Imp7 can funct
ion in two modes. Its Ran-binding site is essential when operating as an au
tonomous import receptor, i.e. independently of Imp beta. Within the Imp be
ta/Imp7 heterodimer, however, Imp7 plays a more passive role than Imp beta
and resembles an import adapter.