Astriking photograph in a cell biology text convinced Ron Milligan (now at the Scripps Research Institute, La Jolla, CA) to take a closer look at the nuclear pore complex, the portal that ships materials back and forth across the nuclear membrane. The shot was the first he'd seen that clearly showed the pore's eightfold symmetry, with structures radiating from the center like petals of a flower, recalls Milligan, then a lab technician with Nigel Unwin's group at the Medical Research Council in Cambridge, UK. Apart from this detail, researchers knew little about the pore's architecture, except that it was a cylinder that sat in a hole spanning the two nuclear membranes, says Milligan. He and Unwin agreed that sophisticated image processing techniques might sharpen this hazy understanding.
They zoomed in on pores—some still embedded in the nuclear membrane and others that they had broken free—using Fourier analysis to enhance the electron micrographs and eke out more structural detail (Unwin and Milligan, 1982). The pair identified four, previously unrecognized pore components: thin rings resembling washers; spokes that clustered inside the rings; a central hub, or plug; and large particles that sometimes sat on the pore's cytoplasmic side. These pieces gave the pore its cylindrical shape, the researchers concluded, with the spokes affixing the complex to the membrane.
Flanked by rings on the cytoplasmic and nuclear sides, the spokes extend inward toward the hub. What the large particles were and what they were doing was a mystery. The researchers raised the possibility that they were ribosomes—and took a lot of grief for it, Milligan recalls. He now thinks they could be structures that collapsed during preparation of the membranes. The central plug was also puzzling—Milligan speculates that it could be material passing through the pore.