Nucleus

In every eukaryote, a tremendous flux of proteins and RNAs of different sizes, shapes, and molecular weights crosses the nuclear envelope barrier segregating the cytoplasm from the nucleus. This flux is accommodated by thousands of enormous 100 MDa transport channels called nuclear pore complexes (NPCs) that are embedded in the nuclear envelopes of all cells. Over the past several decades a complete catalogue of the ~30 subunits termed nucleoporins or nups that build the NPC have been identified along with a blueprint of how they come together to construct the iconic 8-fold radially symmetric NPC. Further, recent advances in cryoelectron microscopy have revealed almost the entire NPC structure from multiple organisms in striking detail. These structures show that all NPCs are not always biochemically the same, rejuvenating long standing questions as to the potential functional specialization of individual NPCs. Likewise, it is now clear that NPCs are surprisingly plastic, capable of constricting and dilating in ways that may be responsive to membrane tension and cellular energy state.

How, or if, these structural rearrangements can be controlled and whether they impact the transport properties of the NPC will be major areas of investigation for the field going forward. Answering these questions, however, will require a more definitive perspective of how the NPC acts as a selective and efficient transport machine. Although amazing progress has been made, there remains much to be learned regarding how the intrinsically disordered proteins that establish both a size-dependent diffusion barrier and selective transport channel for nuclear transport receptors bound to cargo, function in living cells. Collectively answering these fundamental questions will directly inform how NPCs contribute to embryonic development and how continually emerging nup gene variants cause a spectrum of human diseases.

This Article Collection will bring together Original Research, Short Reports, and Reviews that illuminate mechanisms highlighting the central role of the NPC and nuclear transport machinery in cellular and organismal physiology.

Dr. Patrick Lusk is an Associate Professor in the Department of Cell Biology at Yale School of Medicine. He runs the joint LusKing Lab with Dr. Megan King interested in defining mechanisms that maintain the integrity and function of the nuclear envelope system in normal and pathological contexts.

Disclosure Statement: Dr. Lusk declares no conflict of interest regarding this work.

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