Fluorescent probes have revealed that flip-flop of glycerophospholipids, such as phosphatidylinositol (PI), across the membrane of the endoplasmic reticulum (ER) does not depend on the lipid's stereochemistry.

The ER is an extensive membrane system within the cytoplasm of cells made up of glycerophospholipid building blocks. The membrane is self-synthesising and glycerophospholipids are made on the cytoplasmic face and have to be flipped to the other side for the membrane to expand uniformly. The rapid movement of glycerophospholipids across the ER membrane is mediated by specific membrane proteins known as flippases.

In this latest research, Anant Menon from the University of Wisconsin-Madison, US, and colleagues from India and Germany made fluorescence-labelled versions of all four diastereoisomers of PI. The labelled PI molecules were then used as probes to investigate whether the stereochemistry of the inositol or the glycerol parts of PI govern its flip-flop across the ER membrane.

The group found that flippase can transport all four diastereoisomers of PI across the ER without stereochemically selecting the PI molecules that it transports. These findings could have important implications for the hypotheses that the three domains of cellular life originate from a common cellular ancestor.

The immediate challenges of this work are to solve the 3D structure of flippase. Menon believes that this could eventually 'lead to the design of artificial flippases as tools for biotechnological applications and medical treatments'.

Kathryn Sear