Seminar: Sudipta Ashe

Date: 

Tuesday, October 30, 2018, 11:00am to 12:00pm

Location: 

WAB 563

TitleProtein Kinase D regulates secretion of Drosophila Insulin through a Stunted dependent Inter-organ communication from the fatbody

AbstractGrowth and development of metazoan body plan requires a coordinated processes of cell division, migration and differentiation. These processes are regulated at level of gene transcription, translation, post translational modifications and secretion of hormones, growth factors and morphogens that communicate between various cell types. In insects, secreted ligands of the Insulin family (dILPs) promote cellular growth and energy homeostasis which is conserved throughout evolution. Despite these insights, the underlying subcellular processes that control dILP production and release remains poorly understood.

We have identified Protein Kinase D (PKD), as a critical regulator of stimulated hormone production. Inactivating PKD results in impaired larval growth, altered sugar and lipid metabolism manifested by reduced TOR signaling. Inhibition of PKD led to reduced Insulin secretion due to defects in the structure and function of cargo vesicles generated from the TGN (Ashe et al; 2017). Inhibiting PKD in tissue specific manner, in IPCs (Insulin producing cells) and fatbody cells also resulted in similar growth defects with elevated hemolymph-trehalose and lipid levels and altered TOR signaling. Further, constitutively activating PKD also resulted in growth and metabolic impairments which can be attributed to enhanced secretion of Insulin loaded vesicles from the Golgi. Our findings suggests that PKD activity in IPCs and fatbody is required for larval growth by regulating dILP secretion and an Inter-organ communication exists between conventionally secreted fatbody factors and IPCs in orchestrating the complex process of growth. Stunted A (SunA) acts as an endogenous insulinotropic peptide and seems to lead a dual life. We found existence of a Golgi pool involved in insulinotropic activity and is secreted from the fatbody cells in a PKD dependent conventional secretion pathway (Ashe et al; to be submitted). Together, our findings are the first indication that in an organismal context, PKD can regulate metabolism and thus growth and development by controlling Insulin secretion based on its inactivation/activation states, regulating capacity of Golgi to generate vesicles. Our work explored consequences of genetically removing PKD function on IPC exocytosis in an in vivo system and highlights the role of PKD as a regulatory molecule, which can cause Insulinemia under condition of inactivity and Hyperinsulinemia under condition of hyperactivity. Thus, our study can provide valuable insights into the molecular basis of Diabetes.