A proteomic investigation of changes in lipid droplet-bound proteins
EMSL Project ID
2459a
Abstract
Lipid droplets are the body's major location for storing fat to be later used as energy. As such, understanding the regulated function of these droplets is an essential part of understanding metabolism. Our recent proteomic characterization of the proteins present on the lipid droplets, carried out in collaboration with EMSL, demonstrated that the protein composition of Drosophila lipid droplets was largely analogous to that of mammalian droplets, establishing the Drosophila system as a useful model to understand the medically relevant processes in mammals. As part of those recent studies, we uncovered a new and unexpected role for droplets—they store proteins as well as lipids. We found that during early development, histones are sequestered on droplets, likely to prevent the histones from impairing transcription. Later on in development, the histones are released from the droplets and used in the newly formed nuclei to package the additional DNA. A variety of observations, particularly the observation that additional lipid droplets are rapidly formed when cells are stressed (potentially to increase 'buffering capacity'), suggest that this protein storage/sequestration role may be quite general, and an important factor in allowing cells to respond to environmental challenges by either sequestering misfolded proteins, and/or releasing heat-shock proteins. One of the goals of the work proposed here is to investigate this possibility in more detail.In addition to clarifying the role of droplets in protein storage and sequestration, the work proposed will investigate how droplet motion is regulated. Understanding such regulation is important from two points of view. First, our recent work suggests a link between droplet motion and metabolism, so understanding how droplet motion is regulated may ultimately increase our understanding of metabolism. Given the current epidemic of obesity and diabetes, this is certainly pressing. However, understanding regulation of droplet transport is also important from a second point of view: many cargos move bi-directionally, and our work has established that many aspects of bi-directional motion are conserved between different cargos. Thus, understanding regulation of lipid droplet motion at a molecular level will increase our understanding of the motion of many other cargos too. Understanding regulation—and failure of regulation—of cargo transport is relevant for many essential areas of human health, including neurodegenerative diseases such as Alzheimer's.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2007-07-01
End Date
2009-09-30
Status
Closed
Released Data Link
Team
Principal Investigator