From the double membrane enclosing the cell nucleus to the deep infolds of the mitochondria, each organelle in our cells has a distinctive structure that makes it ideally suited to do its job. How these shapes arise, however, is largely a mystery.
Cell biologists at HMS have now determined that just three ingredients are needed to form the complex network of tubules which, together with structures that resemble stacked sheets, make up the internal architecture of the cellular organelle known as the endoplasmic reticulum. The ER makes fat and protein for the cell.
According to Tom Rapoport, an HMS professor of cell biology and leader of the study team, producing the ER’s tubular network is “surprisingly simple,” requiring just three ingredients. The team’s findings were reported online February 22 in Nature.
In addition to answering a longstanding question about basic biology, the findings help explain how certain genetic mutations in ER proteins lead to hereditary progressive muscle disorders of the lower limbs, known collectively as spastic paraplegias.
“Explaining a disease doesn’t mean we can cure it,” says Rapoport, “but it’s gratifying to trace back a complex group of diseases to a molecular defect of individual proteins.”
Tubules are highly curved, with O-shaped cross sections. The researchers found that formation of the ER’s tubular network engages two proteins in a continual tug of war to maintain the right amount of curvature.
Using a simple, yeast-based system they constructed, Rapoport team’s found that either of two protein families—reticulons and REEPs (receptor expression-enhancing proteins)—can stabilize the curvature. The team then figured out that enzymes called GTPases help the tubule membranes stick together to form a network.
Rapoport’s team went on to show that vertebrates may need even fewer ingredients than yeast: a fruit fly GTPase, atlastin, took care of both fusion and curvature stabilization, eliminating the need for a REEP or a reticulon.
Image: Robert Powers and Songyu Wang