Assembly of the Lipid Bilayer in the ER

The ER is the main site for the synthesis of membrane-building lipids, such as phospholipids and cholesterol, and their assembly into the lipid bilayer.

ER embedded enzymes insert newly synthesized phospholipids into the cytoplasmic leaflet of the membrane, expanding it compared to its lumenal counterpart and thus affecting the stability of the lipid bilayer.

As the bilayer grows asymmetrically, calcium-dependent proteins called ER scramblases come into action.

An active scramblase binds calcium ions from the cytosol, opening its hydrophilic groove to pass the polar phospholipid heads from one membrane layer to another.

ER scramblases are non-selective transferring phospholipids with different head groups like choline, serine, or ethanolamine across the lipid bilayer.

Additionally, they are bidirectional and can return phospholipids from the lumenal to the cytoplasmic leaflet, maintaining net membrane growth and stability.

The lipid bilayer assembled in the ER is phospholipid-rich, thin, and fluid to execute specialized functions like vesicular transport and lipid synthesis.

As the membrane gets transported through the endomembrane system, it undergoes further modifications in its composition to suit the needs of the destination organelle.