Chromosomal passengers

Abstract

What are they? Chromosomal passengers are proteins associated with chromosomes during the early stages of mitosis, then with the spindle midzone and equatorial cortex during anaphase and telophase, and finally with the midbody/spindle remnant at the exit from mitosis. It was this unusual dynamic behaviour that first brought INCENP to notice in 1985. Also known as… INCENP, Aurora-B, BIR1/survivin and TD-60. Aliases for INCENP include Sli15p in budding yeast and ICP-1 in C. elegans. Aurora-B is also known in mammals as AIM-1 and Aurora-1, in budding yeast as Ipl1p and as AIR-2 in C. elegans. Survivin is known as BIR1 in both yeasts and C. elegans, and as Deterin in Drosophila.Fig. 1 Most mysterious… TD-60 is a passenger protein, but next to nothing is known about its function. Its localization has been described as a ‘telophase disk’, a distribution seen for all passengers during anaphase/telophase. Whether the disk is a discrete structure or simply a manifestation of the spindle midzone remains a matter of some debate. Not to be confused with… CENP-E, chromokinesin, Polo kinase... A number of proteins are localised a bit like chromosomal passengers. However these proteins occupy slightly different locations on the chromosomes: the kinetochore for CENP-E and Polo; all along the chromosome arms for chromokinesin. Some of these proteins may interact functionally or physically with the passenger proteins. Strangest behaviour… Canonical passenger proteins accumulate in the inner centromeres during metaphase prior to transferring to the spindle midzone at anaphase. If chromosomal passengers do not first concentrate at centromeres, it seems they are not able to move on to the central spindle and midbody later in mitosis. No one knows what is so special about the inner centromere. Who needs them? Chromosomal passengers are essential in eukaryotes from yeast to mouse. INCENP and BIR1/survivin have been knocked out in mouse and budding yeast: result-dead mice and dead yeast. RNAi has shown that INCENP, Aurora-B and Survivin are essential in C. elegans and that the first two are also essential in Drosophila cultured cells. What do they do? The active ingredient in the passenger complex is probably Aurora-B, which apparently phosphorylates a number of important substrates required for chromosome structure, kinetochore function, chromosome bi-orientation at metaphase, and the completion of cytokinesis. INCENP is required for the correct targeting of Aurora-B at all times in mitosis and for Survivin movement to the centromere and all of its spindle and midbody locations late in mitosis. BIR1/Survivin targets Aurora-B during mitosis in C. elegans. Most controversial… BIR1/Survivin seems to love to confound researchers. BIR1/Survivin looks like an inhibitor of apoptosis protein, and dominant-negative mutants can kill cells like nobody's business. In fact, a number of clear and well controlled studies seem to suggest that Survivin may help prevent mitotic cells from apoptosis. However, both yeast and mouse knockouts show pretty convincingly that BIR1/Survivin mutants die, not because of programmed cell death, but because they make a hash of chromosome segregation or cytokinesis. The jury is still out on this one, but at the moment the apoptosis camp looks like they have the most to prove. Where can I find out more BIR1/Survivin-GFP (green) localised to the spindle midzone at anaphase. Image courtesy of Dr. Sally P. Wheatley.