Orbit, a novel microtubule-associated protein essential for mitosis in Drosophila melanogaster

We describe a Drosophila gene, orbit, that encodes a conserved 165-kD micro tubule-associated protein (MAP) with GTP binding motifs, Hypomorphic mutati ons in orbit lead to a maternal effect resulting in branched and bent mitot ic spindles in the syncytial embryo. In the larval central nervous system, such mutants have an elevated mitotic index with some mitotic cells showing an increase in ploidy. Amorphic alleles show late lethality and greater fr equencies of hyperploid mitotic cells. The presence of cells in the hypomor phic mutant in which the chromosomes can be arranged, either in a circular metaphase or an anaphase-like configuration on monopolar spindles, suggests that polyploidy arises through spindle and chromosome segregation defects rather than defects in cytokinesis. A role for the Orbit protein in regulat ing microtubule behavior in mitosis is suggested by its association with mi crotubules throughout the spindle at all mitotic stages, by its copurificat ion with microtubules from embryonic extracts, and by the finding that the Orbit protein directly binds to MAP-free microtubules in a GTP-dependent ma nner.