Question 1

What is the role of flippases in maintaining membrane asymmetry?

Accepted Answer

Flippases are ATP-dependent lipid importers that transfer phosphatidylserine and phosphatidylethanolamine from the outer to the inner membrane layer. As type-IV P-type ATPases, they use energy from ATP hydrolysis to actively pump specific phospholipids across the bilayer, playing a crucial role in generating and maintaining the asymmetric lipid bilayer structure essential for cell function.

Question 2

How do floppases differ from flippases in their transport function?

Accepted Answer

Floppases are ATP-dependent non-specific lipid exporters belonging to the ABC-transporter family that move lipids from the inner to the outer membrane layer, opposite to flippase direction. While flippases selectively transport specific phospholipids inward, floppases transport a variety of phospholipids outward, and together both transporters work to establish membrane asymmetry.

Question 3

What happens when scramblases become activated in erythrocytes?

Accepted Answer

Scramblases are ATP-independent transporters that activate when intracellular calcium ion concentration increases in erythrocytes. Upon activation, they allow random bidirectional movement of phospholipids, transferring phosphatidylserine from the inner to the outer membrane layer. This outward exposure marks cells for eryptosis, a suicidal death pathway, triggering their removal by macrophages.

Question 4

What structural domains do flippases contain and what are their functions?

Accepted Answer

Flippases contain one transmembrane domain with ten transmembrane α-helices and three cytoplasmic domains: a nucleotide-binding domain that binds ATP, a phosphorylation domain that receives the phosphate group, and an actuator domain involved in the dephosphorylation step. These domains work together to enable the ATP-mediated transport of phospholipids across the membrane.

Question 5

How do the two types of scramblases differ in their activation mechanisms?

Accepted Answer

TMEM16F scramblase, located in platelet membranes, requires high calcium ion concentrations for activation. In contrast, Xkr8 scramblase is activated by caspase during apoptosis. Despite different activation pathways, both scramblases perform bidirectional phospholipid transfer without ATP hydrolysis, reducing membrane asymmetry when activated.

Question 6

What disease results from defective scramblase expression?

Accepted Answer

Defective expression of scramblase results in Scott syndrome, a bleeding disorder. Without functional scramblase, cells cannot properly expose phosphatidylserine on their outer membrane during apoptosis or in response to calcium signaling, disrupting normal cell recognition and clearance mechanisms essential for hemostasis.

Question 7

How does ABCA1 floppase relate to cholesterol transport and disease?

Accepted Answer

ABCA1 floppase transfers cholesterol from the inner to the outer membrane leaflet, playing a key role in lipid homeostasis. Mutations in ABCA1 result in Tangier disease, a rare genetic disorder characterized by severely reduced high-density lipoprotein levels and abnormal lipid distribution in tissues.

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