15.18:
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.
15.18:
Assembly of the Lipid Bilayer in the ER
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between membrane leaflets.
Endoplasmic Reticulum Membrane
The ER is the starting point of the secretory pathway. It is involved in producing and shuttling proteins and lipids throughout the endomembrane system. It also synthesizes and distributes the membrane-building phospholipids and cholesterol between membrane leaflets. Most cholesterol molecules are quickly transported from the ER to other cell membranes, leaving behind loosely arranged phospholipids in the ER membrane. As a result, the ER membrane is fluid for transporting and inserting newly synthesized lipids and proteins via the secretory pathway. Additionally, the ER assembles the structural phospholipids into bilayers before they bud off as vesicles to fuse with the membrane of the destination organelle.
Membrane Scrambling
The phospholipids can be non-specifically and bidirectionally translocated between the leaflets of the ER membrane by scramblase proteins.
TMEM16K, a resident ER-membrane protein from the TMEM16 scramblase family, is the only identified ER scramblase. Its activity is affected by the length of the phospholipid acyl tails and calcium concentration in the cell. Thus, it works optimally to transport short-chain lipids, characteristic of the thin ER membranes.
Suggested Reading
- Casares, Doralicia, Pablo V. Escribá, and Catalina Ana Rosselló. "Membrane lipid composition: Effect on membrane and organelle structure, function and compartmentalization and therapeutic avenues." International journal of molecular sciences 20, no. 9 (2019): 2167.