Light at the Ends of the Tunnel

Imagine a tunnel the width of a car, which could expand to grant passage to trucks, and bend when earthquakes shook the ground around it. To find such a tunnel, you need look no further than your own body: there are thousands in each of your cells. Called nuclear pore complexes, these tunnels control traffic in and out of the cell’s nucleus. When scientists in the Beck group at EMBL Heidelberg determined what one of the nuclear pore’s main building blocks – Nup107 – looks like and how it is arranged, they found clues to the tunnel’s flexibility.

“The nuclear pore complex always looks like a perfect ring in the pictures, but in practice we know that it’s not – it’s very floppy,” says Martin Beck. “We found that Nup107 has four hinges where it can bend, to allow this floppiness. There might be two biological reasons for this: it might prevent the pore from breaking if the nuclear membrane is pulled or distorted, and it could also allow the pore to expand a bit to transport very large cargoes.”

Nup107 is shaped like a Y, and scientists at EMBL and elsewhere had been amassing evidence that 8 copies of this Y-shaped piece line up head-to-tail to form the nuclear pore’s ring shape. Khanh Huy Bui and Alexander von Appen, both in the Beck group, discovered that this is not a simple head-to-tail chain. Working with visiting PhD student Amanda DiGuilio, they found that the ring is formed by pairs of pieces, like a chain of tandem bicycles. Eight of these pairs form a ring at either end of the nuclear pore tunnel. This puts the definitive number of Nup107 copies in the nuclear pore at 32, in agreement with a study published earlier this year in which the Beck, Lemke and Bork groups calculated how many copies of each piece make up the nuclear pore.

Once assembled – and unlike most man-made tunnels – nuclear pores are not left permanently in place. They have to be dismantled – along with the membrane they sit in – for our cells to divide. Scientists knew that this disassembly is accomplished by adding phosphate tags to the nuclear pore, and the EMBL researchers have now found that those tags are inserted at the points where the Y-shaped pieces attach to each other, effectively prising apart the tunnel’s building blocks.

In the current study, published recently in Cell, Beck and colleagues used single particle electron microscopy and mass spectrometry to figure out how the molecules within each Y are arranged, and how the Ys connect to each other. They then fitted those pieces into the overall image of the whole ring, which they obtained through electron tomography.