The Remarkable Nuclear Pore Complex

The nuclear pore complex (NPC) is a complicated assembly embedded in the nuclear envelope that has the ability not only to assemble and disassemble quickly, but to adapt to changing needs for transport of macromolecules. The critical function of this elaborate complex has led researchers to invest intensive study, which has recently yielded remarkable new understanding.

In a January 2022 study in Cell, Akey et al. describe resolving the yeast nuclear pore complex to astounding detail. Using both in situ and isolated complexes, they dissect the layered organization of the pore to characterize the flexible inner ring, the adaptin-like central layer, and then the membrane-interacting layer that anchors the complex.

Each of these layers employs complex protein connections that together form “spokes” in the pore. The authors speculate that the multiple layers and flexible connectors provide the means for NPCs to assemble and disassemble as quickly as they do, giving the ability to react to cell cycle stages and environmental conditions.

Interestingly, upon close examination of crystalized structures, the authors observed that yeast has both single and double outer rings. The double outer ring has been observed in two other fungi to date and appears to represent a functional variant.

Upon further examination, the authors identified a third variant in yeast and were able to show that the variants co-exist in cells. One variant has two single outer rings that frame the inner ring, a second form has a single ring on the cytoplasmic surface and a double ring on the nuclear surface (both with nuclear baskets); while a third variant has two single rings, no baskets, and is specifically enriched over the nucleolus.

These variants provide further clues as to how the NPC might assemble as modular structures with multiple forms that adapt to different conditions. Further, the inner ring appears to have the ability to dilate and contract to allow smaller versus larger macromolecules to pass through, thereby adding another means of adaptability.

Understanding the yeast nuclear pore complex provides a foundation for understanding the eukaryotic NPC in general. A paper released this past week by Petrovic et al. in Science looked closely at just this set of relationships, comparing the human NPC to both the S. cerevisiae and Chaetomium thermophilum fungal NPCs. They show how, despite low conservation of sequence among nucleoporins and the other components of the pore complex, there is strong evolutionary conservation of the linker-scaffold architecture between humans and fungi. Once more, studies on model organisms throw bright light on the inner workings of our own cells.