Protein folding and quality control during nuclear transport

The spatial separation of protein synthesis from the compartmental destiny of proteins led to the evolution of transport systems that are efficient and yet highly specific. Co-translational transport has emerged as a strategy to avoid cytosolic aggregation of folding intermediates and the need for energy-consuming unfolding strategies to enable transport through narrow conduits connecting compartments. While translation and compartmental translocation are at times tightly coordinated, we know very little about the temporal coordination of translation, protein folding, and nuclear import. Here, we consider the implications of co-translational engagement of nuclear import machinery. We propose that the dynamic interplay of karyopherins and intrinsically disordered nucleoporins create a favorable protein folding environment for cargo en route to the nuclear compartment while maintaining a barrier function of the nuclear pore complex. Our model is discussed in the context of neurological disorders that are tied to defects in nuclear transport and protein quality control.