Current Research Projects in the Lab:
Through our studies of the golgin protein Lava Lamp (LVA) we have established that a significant amount of
the plasma membrane growth required for cell formation in Drosophila embryos requires de novo Golgi-dependent
membrane secretion (Papoulas et al., 2005; Sisson et al., 2000). Golgin proteins were originally identified as
human autoantigens implicated in a variety of human autoimmune diseases (Chan and Fritzler, 1998) and are thought
to function on the surface of Golgi bodies as scaffolds for Golgi structural integrity and tethers for specific
membrane transport vesicles or the cytoskeleton (Short et al., 2005). We have shown that LVA functions as an
adaptor for the microtubule (MT) motility factors cytoplasmic Dynein, Dynactin, and CLIP-190, the Drosophila
ortholog of CLIP-170 (Figure 2)(Papoulas et al., 2005). Together these proteins target Golgi bodies towards
the minus-ends of MTs and the embryo’s surface to facilitate secretion of new plasma membrane required for
cleavage furrow formation (view movie )(Papoulas et al., 2005). One of our current research priorities is to test
whether LVA functions as a molecular switch to turn on and off Dynactin-dependent, Dynein-driven movement of Golgi
bodies in live embryos.
Mechanisms of membrane transport required for cell formation.
We have also begun to investigate the role of LVA during later stages in development. These studies have demonstrated that LVA is required in somatic cells for viability and female fertility. We know that diminished LVA activity in somatic cells of adult females blocks oogenesis, and we are now in the process of establishing the cellular basis of this effect (Figure 3).
A screen of an existing collection of temperature sensitive (ts) mutants for defects in cleavage furrow formation using time-lapse differential interference contrast (DIC) microscopy of live mutant embryos has identified at least one gene required for membrane secretion. A total of five mutants were found that display robust defects within minutes of shifting live embryos to the restrictive temperature. Four of these mutations exist in genes that have not been previously implicated in cleavage furrow formation. Our analysis of one of these four mutants, which we have named inferno, suggests it disrupts the early secretory pathway (Figure 4). Our future characterization of inferno and the other four mutants should provide a more complete understanding of the molecular mechanisms controlling cleavage furrow formation. Drs. Helen Francis-Lang and William Sullivan kindly provided the mutant collection for this project.