31. Biological membranes

The cell membrane is comprised of lipids, proteins and carbohydrates. Lipids provide structure, proteins provide function while carbohydrates facilitate cell to cell communication.

Lipids

The role of PIP2 in the PKC pathway.

The cell membrane is made up of two layers of lipids, each layer being called a leaflet. The layer in contact with the cytosol is the cytosolic leaflet while the layer in contact with the extracellular space is the outer leaflet. The main types of lipids membranes are comprised of are glycerophospholipids, sphingolipids and cholesterol. Glycerophospholipids are derivatives of glycerol 3-phosphate.

Some membrane lipids are involved in intracellular signaling, especially PIP2. The receptor for many hormones activate PLC. Phospholipase C cleaves a lipid called PIP2 into IP3 and DAGs. IP3 will bind to its receptor on the ER membrane and cause efflux of Ca2+ from the ER into the cytosol. This Ca2+, together with DAG will activate PKC.

PIP2 is also involved in the insulin pathway. After insulin has bound the insulin receptor, an enzyme called PI3K will be activated. PI3K will phosphorylate PIP2 to PIP3, which in turn will activate PDK1, the next kinase in the pathway.

Proteins

This figure shows how lipids can be flipped or flopped from one side of the membrane to the other. PE is phosphatidyletanolamine and PS is phosphatidylserine.

Many transmembrane proteins are transporters, either transporting things into or out of the cell. Three classes of transporters are important. Flippases move lipids like phosphatidylserine and phosphatidyletanolamine from the outer leaflet to the inner, while floppases move them in the opposite direction. Scramblases move them in either direction.

Many types of ATPases exist. Flippases are a type of ATPases called P-type ATPases. Other subtypes of P-type ATPases are the Na+/K+ ATPase and the H+/K+ ATPase, for example.

The proton pumps that pumps proton into lysosomes to make them acidic are V-type ATPases.

The ATP synthase in the mitochondria is an F-class ATPase.

The floppase belongs to an ATPase family called the ABC superfamily. The CFTR ion channel also belongs to this family.

Aquaporins are water transporters. We only have to know one type, the AQP-2, which is phosphorylated and activated by PKA in response to the hormone vasopressin.