The Role of βFTZ-F1 and MMP2 in Regulating Hormone-Mediated Autophagy and Insulin Signaling in the Drosophila Fat Body
Date
2014-06-02
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
All animals transition through several different stages during their
development. Three major processes are involved in regulating the progression
from one developmental stage to the next: cell growth, nutrient utilization and cell
death. In Drosophila melanogaster, distinct developmental changes occur during
feeding and non-feeding periods. The larval stage is characterized by extensive
feeding, while metamorphosis involves a long period of starvation (Aguila et al.,
2007).
Insulin signaling is a highly conserved pathway that has long been known
to play a role in regulating growth, nutrient storage and metabolism. Nutrient
storage during the larval stage occurs primarily in the larval fat body, which
functions as a hybrid of the mammalian adipose tissue and liver, and allows for
the rapid growth of the animal (Britton et al., 2002).
As the animal enters metamorphosis, insulin signaling has to be shut off to
allow for the breakdown of stored nutrients via autophagy- a conserved catabolic
pathway that targets cytoplasmic constituents for degradation. Even though it is
known that autophagy and insulin signaling are antagonistic processes, the
molecular mechanisms that regulate these two mutually exclusive processes have
not been fully characterized (Scott et al., 2004).
Fly metamorphosis is regulated in large part by the steroid hormone 20-
hydroxyecdysone (20E). While most larval organs are destroyed by massive cell
death during metamorphosis, the larval fat body escapes this fate and is instead
remodeled from a sheet of attached polygonal cells into individual cells that
disperse throughout the developing body, providing nutrients. Specifically, a
proteinase called matrix metalloproteinase-2 (MMP2) is responsible for the
proteolytic degradation of the extracellular matrix and dissociation of the fat body
cells. Previous studies have suggested that MMP2 is a potential downstream target
of the βFTZ-F1 mediated, 20E signaling cascade. βFTZ-F1 is a nuclear receptor
that is required to confer competence upon tissues to respond to 20E (Bond et al.,
2011).
In this study, I examined the role of MMP2 and βFTZ-F1 in regulating
hormone-induced autophagy and insulin signaling. I hypothesize that MMP2, in
addition to functioning in fat body remodeling, also downregulates insulin
signaling during metamorphosis, thus triggering nutrient release by autophagy.
Moreover, I hypothesize that βFTZ-F1 promotes autophagy in the fat body during
metamorphosis. To test these hypotheses, I performed mosaic analyses with
reduced βftz-f1 and MMP2 expression and looked for the presence of
autophagosomal structures. I have demonstrated that βFTZ-F1 is required for
autophagy during metamorphosis, while MMP2 does not seem to play a
significant role in the regulation of autophagy during this stage.
Description
Keywords
steroid hormones, autophagy, insulin signaling, βFTZ-F1, MMP2