Crumbs, Galla and Xpd are required for kinesin-5 regulation in mitosis and organ growth in Drosophila

Abstract

Xeroderma Pigmentosum D (XPD) is a multi-function protein involved in transcription, DNA repair, and chromosome segregation. In Drosophila, Xpd interacts with Crumbs (Crb) and Galla to regulate mitosis during embryogenesis. It is unknown how these proteins are linked to mitosis. Here, we show that Crb, Galla-2 and Xpd regulate nuclear division in syncytial embryo by interacting with Klp61F, the Drosophila mitotic kinesin-5 associated with bipolar spindles. Crb, Galla-2 and Xpd physically interact with Klp61F and co-localize to mitotic spindles. Knockdown of any of these proteins results in similar mitotic defects. These phenotypes are restored by overexpressing Klp61F, suggesting that Klp61F is a major effector. Mitotic defects of galla-2 RNAi are suppressed by Xpd overexpression but not vice versa. Depletion of Crb, Galla-2 or Xpd results in a reduction of Klp61F levels. Reducing proteasome function restores Klp61F levels and suppress mitotic defects caused by knockdown of Crb, Galla-2 or Xpd. Further, eye growth is regulated by Xpd and Klp61F. Hence, we propose that Crb, Galla-2 and Xpd interact to maintain the level of Klp61F during mitosis and organ growth.