The Arf GAP Asap regulates cleavage furrow biosynthesis in the early Drosophila embryo

Plasma membrane (PM) growth is a common feature of eukaryotic cells. For cells to grow and divide newly synthesized membrane needs to be inserted into their existing PM. Failure to do so may lead to developmental disorders and disease in animals. In the early Drosophila embryo, ingression of cleavage furrows during syncytial divisions is fueled by the insertion of new membrane into the apical domain via the biosynthetic secretory pathway. The highly conserved small G protein Arf1 regulates biosynthetic trafficking at the Golgi. Arf1 activity is regulated by Arf guanine nucleotide exchange factors and GTPase activating proteins (GAPs). However, the essential roles of Arf GAPs during development remain unclear. Here I demonstrate that the Arf GAP Asap is required for cleavage furrow ingression in the early Drosophila embryo. Asap primarily promotes Arf1 function at the Golgi. Asap is required and sufficient for Arf1 accumulation at the Golgi, and a conserved Arf1-Asap binding site is required for Golgi organization and output. Interestingly, Asap shifts localization during the cell cycle, and relocalizes to the nuclear region at metaphase. This shift coincides with a mild reorganization of the Golgi, and a natural phase of furrow regression. Together these data reveal an Asap-Arf1 regulatory pathway required for Golgi-dependent cleavage furrow biosynthesis. Asap may recycle Arf1 to the Golgi from post-Golgi membranes, providing optimal Golgi output for specific stages of the cell cycle. The results of this study may further our understanding of Asap function in cancer and other diseases.Ph.D.2019-11-07 00:00:0