Passenger proteins check in

D espite their name, the passenger proteins aren't just along for the ride during mitosis. They are busy helping control the attachment of spindle fi bers to the chromosomes and ensuring that the cell splits after the chromosomes part. INCENPs' many locations But it was the proteins' seemingly bizarre movements that fi rst caught the eye of William Earnshaw (now at the University of Edinburgh in the UK) and his colleagues in 1987. Previous work had demonstrated that sister chromatids can separate even when researchers cut the microtubules that form the spindle, suggesting that the centromere might house motors that propel the chromosomes. But cell biologists knew little about the centromere's architecture. In 1985, Earnshaw's lab snared the fi rst three of the structure's components, which they dubbed the centromere proteins, or CENPs (Earnshaw and Rothfi eld, 1985). Using antibodies against the chromosomes' protein scaffold, Carol Cooke then identifi ed a pair of proteins that cluster on the centromere. The Edinburgh team called this pair the inner centromere proteins, or INCENPs (Cooke et al., 1987). Earnshaw and colleagues could see INCENPs clinging to the arms and centromere in mi-totic chromosomes. They took a closer look, treating cells so that the chromosomes were spread-eagled into the textbook " X " shape. They saw that some INCENPs adhered to the centromeres internal to the CENPs at the last points of contact between sister chromatids. Biochemical tests indicated that the INCENPs clung tightly to the chromosome's protein scaffold, so the researchers got a jolt when they tracked the proteins through mitosis. At the beginning of anaphase the INCENPs appeared to jump ship. Instead of following the chromosomes as they slid apart to the poles, the proteins festooned the microtubules in the middle of the mitotic spindle. And some snuggled up to the cell membrane at the point where the cleavage furrow later squeezes the cell in two. " Nobody had seen a chromosomal protein change its position that dramatically, " says Earnshaw. He and his colleagues had identifi ed the fi rst passenger protein (the two INCENPs turned out to be splice variants of the same molecule). INCENP concentrated at the site of presumptive cleavage furrow formation before myosin appeared there (Eckley et al., 1997), making it tempting to speculate that it was being dropped at the site after hitching a ride on the chromosomes as a " passenger. " But earlier functions …