12.6 : Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.

Flippase

Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one transmembrane domain containing ten transmembrane α-helices and three cytoplasmic domains. The three cytoplasmic domains include a nucleotide-binding domain, a phosphorylation domain, and an actuator domain involved in the dephosphorylation step.

Floppase

Floppases belong to the ATP-binding cassette or ABC-transporter family proteins that transfer a variety of phospholipids from the inner to the outer leaflet of a membrane. Some of the essential proteins of this family are ABCA1, ABCA4, ABCB1, and ABCB4. ABCA1 floppase can transfer cholesterol from the inner to the outer leaflet of the membrane, and its mutation can result in Tangier disease.

Scramblase

Scramblase, unlike flippase and floppase, can do the bidirectional transfer of phospholipids in the membrane without using energy from ATP hydrolysis. There are two types of scramblases in the cell - transmembrane protein 16F (TMEM16F) and XK-related protein 8 (Xkr8). TMEM16F scramblase is located within the platelet membrane and needs a high concentration of calcium ions for activation. In contrast, caspase activates Xkr8 in the cell membrane during apoptosis. The defective expression of scramblase results in a bleeding disorder called Scott syndrome.