Mms19 promotes spindle microtubule assembly in neural stem cells through two distinct pathways

Abstract

Mitotic divisions depend on the timely assembly and proper orientation of the mitotic spindle. Malfunctioning of these processes can considerably delay mitosis, thereby compromising tissue growth and homeostasis, and leading to chromosomal instability. Here we identified Mms19 as an important player in these processes as it promotes spindle and astral microtubule (MT) growth and consequently regulates spindle orientation and mitosis duration in Drosophila neural stem cells. Loss of functional Mms19 drastically affects the growth and development of mitotic tissues in Drosophila larvae. We found that Mms19 performs its mitotic activities through two different pathways. By stimulating the mitotic kinase cascade, it triggers the localization of the MT regulatory complex TACC/Msps (Transforming Acidic Coiled Coil/Minispindles, the homolog of human ch-TOG) to the centrosome. In addition, we present evidence that Mms19 stimulates MT stability and bundling by binding directly to MTs.