Individual subunits can then recycle by becoming straighter following the exchange of GDP for GTP. (left) The newly activated subunits form a sheet that will soon zip up to form the tubular polymer. (right)

Nogales's insight into microtubule disassembly, also called depolymerization, has shed new light on a long-standing puzzle in cell biology: How do microtubules manage to pull chromosomes to the poles in a dividing cell, even though the chromosomes attach to the end of the microtubule that is falling apart. As Nogales puts it, "the kinetochore [a large complex of proteins that acts like a dock for the chromosome to connect with the microtubule] is grabbing onto the microtubule, but the microtubule starts breaking down. So it's like grabbing onto a rope that is burning. Yet somehow the chromosomes are being pulled instead of falling off."

Her revelation came from two key pieces of data. First, her group characterized how the microtubules break down, defining how the columns of the polymer peel back, a bit like the peels of a banana. Second, by studying a key kinetochore complex in budding yeast, they observed that about 16 copies of the complex snap into a ring around the microtubule. When microtubules start fraying apart, with their ends curling backward, the fraying action pushes the ring, which then slides along the intact portion of the microtubule, toward the edge of the cell, taking the chromosome with it.

Nogales made her film before she and her collaborators discovered the kinetochore ring. Even so, she says, having the movie makes it easier for people to understand how the system might work. "When you see something moving, you get a feeling of motion in your brain that you don't get from seeing a picture," she says. "Now the only thing we have to do is tell them to imagine a ring around the microtubules, and they see what will happen."

With audiences following her work more completely, Nogales says the value of the movie far exceeds what she paid for it. The company that made it was still testing its product, and so charged her only $5,000. The real cost for the time-intensive project (it took about 2 months of twice-weekly meetings with the filmmakers) would have been $50,000. At that rate the company couldn't find any takers and closed its doors. Although she's not sure if NIH or HHMI would agree, Nogales says even that fee might not be too much. She expects her movie to be useful for several years to come, adding, "It was the best $5,000 I've ever spent."

Images: Nogales Lab

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