Chapter 1: Cell Physiology and Structure
What is the function of the various phospholipids that compose the lipid bilayer of cell membranes?
(A) Separate the intracellular space from the extracellular space
(B) Serve as substrates for the formation of signal transduction molecules
(C) Serve as signals to induce the phagocytosis of apoptotic cells
(D) Serve as a boundary between aqueous and nonaqueous components
(E) Although phospholipids are commonly thought of only as the structural components of the cell membrane, they serve many signaling functions as well.
The formation of the phospholipid bilayer plasma membrane results in the separation of the intracellular space from the extracellular space and controls the permeability of the cell to ions and molecules. The inclusion of cholesterol and glycolipids in the phospholipid bilayer additionally enhances the barrier properties and modifies the fluidity of the membrane. Thus, one of the main functions of phospholipids is to provide a fluid barrier between the cytosol and the extracellular environment.
However, many phospholipids in the plasma membrane also serve as substrates for cell signaling, primarily in the conversion of extracellular signals to intracellular signals. Phosphatidylinositol 3′-kinase (PI3K) is a lipid kinase that phosphorylates inositol phospholipids, derivatives of phosphotidylinositol, to transmit intracellular signals in response to growth factors and cytokines. Phospholipases are another example of enzymes in the plasma membrane that are activated in response to a variety of extracellular ligands. Phospholipase A cleaves arachidonic acid (AA) or its relatives from the 2-position on membrane phospholipids to result in the eventual formation of inflammatory leukotrienes and prostaglandins. Phospholipase C cleaves an inositol phospholipid (i.e., PIP2) on the cytosolic side of the plasma membrane to form two fragments 1,2-diacylglycerol (DAG) and IP3. DAG remains in the membrane to activate protein kinase C (PKC), and cytosolic IP3 stimulates the release of Ca2+ from the endoplasmic reticulum (ER). PKC remains bound to the cytosolic side of the plasma membrane where there is a concentration of negatively charged phosphatidylserines, which are necessary for its activity. PKC and cytosolic Ca2+ are involved in many signaling functions of the cell.
The asymmetrical distribution of the charged phosphatidylserine molecules are also used to distinguish cells that have undergone apoptosis. Phosphatidylserines are normally maintained on the cytosolic side of the plasma membrane in living cells. The altered activities of phospholipid translocators in apoptotic cells results in the translocation of phosphotidylserines to the outer face of the cell membrane. The exposed phosphotidylserines serve as signals to induce the phagocytosis of apoptotic cells by macrophages.