The groups of David Savage (Institute of Metabolic Sciences) and Symeon Siniossoglou (CIMR) have collaborated in a Developmental Cell study that provides new insights into a biophysical mechanism through which levels of the major membrane component phosphatidylcholine (PC) are sensed.
The physiological importance of maintaining membrane lipid composition within narrow limits is reflected by the many diseases in which this process is disrupted. How cells regulate cholesterol levels is relatively well understood but exactly how phospholipid levels are controlled is less clear.
They showed that PCYT1A, the rate-limiting enzyme in the Kennedy pathway for PC synthesis, is confined to the nucleus. By combining lipidomics, data modelling and functional studies across yeast, flies and mammalian cells, they propose a model in which PCYT1A senses changes in the surface topology of the inner nuclear membrane and alters PC synthesis accordingly. Exactly why this key regulatory step takes place inside the nucleus remains unclear.