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The Regulation of Toll-signaling by the Sbf complex in D. Melanogaster

  • Author(s): Saluja, Abhishek
  • et al.
Abstract

Membrane trafficking is the process of intracellular transport of cargo in vesicles. Cells are highly compartmentalized, and thus regulate necessary functions through trafficking. Phosphoinositides and Rab GTPases are important components that are trafficked. Our lab has identified a phosphoinositide and Rab GTPase co-regulatory complex called the Sbf complex. The Sbf complex has specific functions in endosomal trafficking. The Toll- signaling pathway is known to induce the formation of melanotic masses (tumors) upon hyper-activation. The discovery of masses in fly macrophages (hemocytes) while studying the Sbf complex led me to study the impact of modulating the Sbf complex on Toll-signaling, with the goal of identifying mechanisms of Sbf complex function. I show here that over-expression and loss of function of the Sbf complex led to mass suppression in third instar Drosophila larvae. While the Toll protein levels were unchanged with loss of function of the Sbf complex, the endocytosis of Toll differed in each condition. The level of Toll endocytosis was different when individual members of the Sbf complex were depleted. This difference in endocytosis of Toll is shown in both hemocytes and fat body (liver). In addition, our lab has shown that the Sbf complex is required for proper autophagosome trafficking, a key step in autophagy, the process of degrading cytoplasmic materials in the lysosome. Here I also show how depletion of a key autophagic gene led to mass suppression. This indicated the potential impact of autophagy on the Toll-signaling pathway. These studies suggest that the impact of the Sbf complex on Toll- signaling could be at the level of Toll endocytosis and/or an autophagy-dependent response. In addition to understanding mechanisms of Sbf complex functions, these findings show that key steps of the autophagic process could potentially be necessary for the signal to be fully transduced along the Toll-signaling pathway

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