Fig. 7.

Models of lipid loading into non-membrane proteins, like SF-1. Steps labeled with “?” are not known to occur, all other steps are well established to occur. Classically, 1A) only signal-containing nascent peptides are translated on rough ER, however 1B) many nuclear proteins are translated on membrane-bound ribosomes, where 2) folding nuclear proteins may sense the ER lipid content while attaining mature structure 3) then carry that information into the nucleus 4). SF-1 is able to exchange lipids with membrane systems in vitro 5) this may happen in cells, although no data exist. Equilibrium concentration fluctuations in membrane lipids 6) may allow varying sensitivity to signaling enzymes such as IPMK and PTEN. Phosphoinositide transfer proteins 7) mediate lipid movement between membrane systems, but it is not known if they aid in loading lipids into non-membrane proteins, aiding in equilibration 8).