Lecture 18 - Cell biology of lipids and membrane microdomains Flashcards

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1
Q

What are the 4 major phospholipids?

A

Phosphatidylserine

Phosphatidylcholine

Phosphatidylethanolamine

Sphingomyelin

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2
Q

What can be said about the lipid content of different compartments?

A

Different compartments of a cell have different membrane compositions. ER contains higher concentrations of PC and PE.

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3
Q

What is unique about the lipid composition of the plasma membrane?

A

PM contains higher concentrations of cholesterol and Sphingomyelin.

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4
Q

Are lipid bilayers typically symmetrical?

A

The bilayers are not symmetrical and most lipids exposed to extracellular space (and topological equivalents) have a different composition to those exposed to the cytosol.

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5
Q

What phospholipids are more common on the cytosolic side?

A

PE, PS, and PI

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6
Q

What phospholipids are more common on the extracellular side?

A

PC, SM and glycosphingolipids

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7
Q

How can positioning of phospholipids assist in apoptosis?

A

Phosphatidylserine exposes itself to upper leaflet during apoptosis which signals phagocytosis by phagocytes.

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8
Q

What are the effects of cholesterol on the plasma membrane?

A

Decreases mobility of adjacent phospholipis molecules.

Decreases membrane fluidity

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9
Q

Where can cholesterol be found?

A

Most is found in PM >80% and it is found in both leaflets.

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10
Q

What is a lipid raft?

A

Lipid raft is the result of having an ordered lipid bilayer surrounded by disordered bilayer. This is because it contains a lot of cholesterol and saturated fatty acids.

Lipid rafts are thicker in PM than the rest of the membrane and more proteins are found in lipid rafts. (GPI anchored proteins) Hydrophobic domains of proteins tend to associate with lipid rafts.

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11
Q

What are the benefits of having lipid rafts on cell membranes?

A

Rafts can selectively incorporate or exclude proteins thereby governing protein - protein and protein - lipid interactions.

Lipid rafts are also important for efficient receptor signalling.

Sorting and vesicle formation.

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12
Q

What is the evidence for lipid domains?

A

Analysis of liposomes: In-vitro liposomes shows that some lipids self-associate in liquid-ordered domains or rafts.

Detergent insolubility: Detergents solubilise the lipid rafts least preferably. (centrifuging resulting mixture results in lipid rafts to be measurable and observable)

Biophysical measurements: Atomic force microscopy shows peaks where rafts are found with GPI anchored proteins almost exclusively being found near them.

Microscopic evidence: toxin was used to attach to some GM1 (a glycosphingolipid), PLAP (a GPI), and TfR (a protein receptor) fluorescent molecules and as a result lipid rafts were identified.

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13
Q

What are caveolae and how are they formed?

A

Caveolae provide an endocytic vesicle and they don’t use protein coats to be made. Caveolin is the protein that allows this form of endocytosis to occur.

Caveolin has a hairpin shape which induces bends in the membrane inducing formation of the caveolae vesicles.

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14
Q

What is an example of a mechanism by which vesicles can be formed without accumulation of a coat protein?

A

Chemical modification of fatty acid in a plasma membrane can induce the bends required to create a vesicle. Endophilin 1 is a protein that abuses this and induces bending of the membrane by modifying fatty acids in the membrane this results in vesicle formation.

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15
Q

What are phosphatidylinositols?

A

A minor class of membrane phospholipids that are responsible for an enormous number of membrane mediated cellular processes.

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16
Q

Why are PIs highly localized?

A

Phosphatidylinositols have highly localized distributions due to activity of a large family of lipid kinases and phosphatases.

17
Q

Why can PIs adopt a variety of shapes?

A

PIs can contain phosphate at various sites. This results in different shapes and different variations can result. Their concentrations vary in different structures. The reason for the variety in localization is due to the location of the modifying enzymes. This creates a different code for a different membrane lipid.

18
Q

What is the significance of the abundance of binding sites found on phosphatidylinositols?

A

Proteins can discriminate between different PIs via lipid binding molecules or domains.

19
Q

How do vesicles use phosphatidylinositols to fuse with the correct endomembrane compartment?

A

Many proteins bind to specific PI lipids via lipid binding modules this prevents incorrect fusion of vesicles with ER or golgi.

20
Q

How do proteins tell when they have arrived at the correct destination

A

FYVE - proteins tether transport vesicles to endosomes and allow interactions to occur between proteins of transport vesicle and target membrane (specifically for endosomes)