Navigating The Nuclear Envelope: One Or Multiple Transport Mechanisms For Integral Membrane Proteins?

Several different mechanisms have been proposed for how membrane proteins access the inner nuclear membrane. These include mechanisms using both the central and peripheral channels of the nuclear pore complexes that involve free diffusion in the membrane, directional transport using transport receptors, directional transport with inner nuclear membrane proteins acting as their own transport receptors, an ATP-dependent process, and mechanisms involving membrane fusion. However, whether the differences reported reflect fully distinct mechanisms, different licensing steps for the same fundamental mechanism, or artifacts of experimental manipulation remains unclear. It is also reasonable to postulate that the hardware for multiple mechanisms exists but that some are backup mechanisms only used if the primary mechanism fails. If such is the case, there is also to consider the biological context, nuclear pore architecture, abundance of relevant proteins and motifs, and energy expenditure for different or competing mechanisms. Here, we evaluate existing data supporting these proposed mechanisms in context of these factors, the milieu of inner nuclear membrane proteins and evolution.