Chromosomal passengers: toward an integrated view of mitosis

Abstract

The major events of mitosis have traditionally been considered to represent two distinct pathways and have been studied by two separate groups of workers. The chromosomal events (chromosome condensation and sister chromatid disjunction) have been the principal focus for one group, while the cytoskeletal events (nuclear envelope breakdown, chromosomal movements, cytokinesis) have been the focus for the other. This historical division is epitomized by the view of many cell biologists, which was aptly caught by Mazia's comparison of the role of the chromosome arms in mitosis to that of "the corpse at the funeral" which "provide a reason for the proceedings but do not take an active part in them" (Mazia 1961). More recent studies have demonstrated that the role of the chromosomes in mitotic movements is somewhat more active than this. That the kinetochore may play an important role in chromosome movements has long been suspected (see early references in Mazia 1961) but was only proven rather recently (Brinkley et al. 1988; Gorbsky et al. 1987; Nicklas 1989). This has led to a burst of recent interest in all aspects of kinetochore structure and function. Our studies have led us to ask whether chromosomes may play an even more extensive role in the events of mitosis. We suggest here that in addition to their active role in movements, the chromosome may make important structural contributions to the anaphase spindle and cleavage furrow, which are normally thought of as "cytoskeletal" functions. These structural contributions may be made by members of a new class of "chromosomal passenger" proteins that use the chromosomes as a means of conveyance so that they are correctly positioned at the metaphase plate to carry out their nonchromosomal functions during anaphase and the subsequent mitotic events.