A research team in the College of Science has revealed how cells move lipids — essential fats — between membranes, a process fundamental to brain health, metabolism and immunity.
Published in Nature, the study was led by Sarah Clark, assistant professor of biochemistry and biophysics. Her team determined the detailed structure of a massive lipid transport protein called LPD-3, showing how it forms a tunnel to transport lipids between compartments within the cell. The team also identified two new helper proteins, including one they named Spigot, that they plan to study further.
“The study focused on understanding how bridge-like lipid transport proteins work,” Clark said. “It’s a class of lipid transport protein that has recently been discovered in the last six years. And it turns out it is absolutely fundamental for transferring lipids throughout the cell.”
These proteins help cells replenish lipid membranes around organelles like mitochondria and nuclei, membranes that are constantly changing due to processes like endocytosis and exocytosis.
“Most of the lipids are made in the endoplasmic reticulum and then they have to get to the plasma membrane, the mitochondria and all of these different organelles. This has to be done quickly and almost constantly,” Clark said.
Her team genetically modified C. elegans, a type of roundworm often used as a model organism, to isolate protein complexes. Traditional techniques had proven difficult because LPD-3 is large — more than 4,000 amino acids.
While doing this, the researchers unexpectedly found that LPD-3 co-purified with other proteins, meaning they were physically attached to the complex and pulled out during the same process. Two were previously unknown: Spigot and a second protein the team temporarily dubbed LTAP2 (Lipid Transfer Auxiliary Protein 2).
“We had no expectations,” Clark said. “We might have just purified LPD-3 on its own, but instead it co-purified with these two other proteins, neither of which has been characterized, which was brand new and exciting.”
