View Program - 63rd Annual Drosophila Research Conference

In humans, Bcl-2-associated athanogene 3 (BAG3) is essential for proteostasis in stressed cells. Some of the known functions of BAG3 include promoting chaperone activity, facilitating aggresome formation, and initiating the destruction of proteins via macroautophagy. Our lab has discovered that Drosophila Starvin (Stv), the ortholog of mammalian BAG3, biochemically and genetically interacts with the evolutionarily conserved NUAK serine/threonine kinase, and this NUAK-Stv-Hsc70-4 complex plays a role in the autophagic clearance of proteins. However, the mechanism of how damaged proteins get transported to the sites of degradation is not clear. Based upon literature in neuronal cells that describe a role for the Striatin Interacting Phosphatase and Kinase (STRIPAK) complex in the axonal transport of autophagosomes, we propose the hypothesis that the STRIPAK complex may be required to transport proteins along microtubules (MTs) to the lysosome in Drosophila larval muscles. To test for a possible role of the supramolecular STRIPAK complex in BAG3-mediated transport, we have employed a sensitized genetic assay using RNA interference (RNAi) technology. Thus far, our data shows that stv genetically interacts with genes that encode for some members of the STRIPAK protein complex, including Striatin interacting protein (Strip1), MOB kinase activator 4 (Mob4), and Connector of kinase to AP-1 (Cka). Moreover, preliminary observations suggest perturbations in the MT network within muscle cells upon RNAi knockdown of STRIPAK complex members. This project will give us a better understanding of how the NUAK-Stv-Hsc70-4 complex functions with STRIPAK complex in the autophagic clearance of protein and maybe lead to finding some potential drug targets for treating protein aggregate diseases in human.

The STRIPAK complex and microtubule protein transport in Drosophila muscle tissue