Membrane Microdomains + Making domains

Raft disruption

Rafts can be disrupted by detergents, which specifically extract cholesterol from membranes.

• Indicates the importance of cholesterol in maintaining the integrity of lipid rafts

Raft fractions

Contain a subset of plasma-membrane proteins, many of which are implicated in sensing extracellular signals and transmitting them into the cytosol

Integral membrane proteins

Span a phospholipid bilayer and contain one or more hydrophobic membrane spanning domain

• Contain many hydrophobic amino acids whose side chains protrude outward and interact with the hydrophobic hydrocarbon core of phospholipid bilayer

• Consist of one or more alpha helices or multiple beta strands

Alpha helices in bilayers

Stably embedded in membranes energetically favourable hydrophobic and Van der Waals interactions of the hydrophobic side chains in the domain with specific lipids

Peripheral membrane proteins

Do not directly contact the hydrophobic core of the phospholipid bilayer. They are instead bound to the membrane either indirectly by interactions with integral or lipid anchored membrane proteins or directly with interactions with polar head groups

Peripheral proteins (cytosolic side)

They may link the membrane to the cytoskeleton, supporting various membranes and dictating shape and mechanical properties

• Play roles in cell signalling and cellular communication by acting as receptors or signalling molecules.

Peripheral proteins (outer surface)

Often attached to components of the extracellular matrix or to the cell walls surrounding bacterial cells

• Provides crucial interface between the cell and its environment

Lipid anchored membrane proteins

Bound covalently to one or more lipid molecules. Hydrophobic tail of the attached lipid is embedded in one leaflet of the membrane and anchors the protein to the membrane.

• Polypeptide chain itself does not enter the phospholipid bilayer

Caveola

Small, flask shaped invaginations of the plasma membrane, particularly abundant in vascular endothelium and other cell types like vascular smooth muscle cells

• Enriched in cholesterol and glycosphingolipids and associated with proteins called caveolins

Water-soluble precursor

A chemical compound that readily dissolves in water and can serve as the starting material for a chemical reaction or process

• Can be converted into membrane lipid products which are critical for maintaining the proper composition and properties of membranes and overall structure

Cell membrane synthesis

• Cells synthesise new membranes only by the expansion of existing membranes

• Early steps take place in the cytosol, but the final steps are catalyzed by enzymes bound to pre-existing cellular membranes

Small cytosolic fatty acid-binding proteins

Facilitate movement of fatty acids, transport the fatty acids through the cell cytosol

Phosphatidylcholine production Step 1

• Two fatty acids synthesised on fatty acyl CoA - esterified to the phosphorylated glycerol backbone, forming phosphatidic acid

• Hydrocarbon tails anchor the molecule to the membrane

Phosphatidylcholine production Step 2

Phosphatase - converts phosphatidic acid into diacylglycerol by removing a phosphate

Phosphatidylcholine production Step 3

Phosphotransferase transfers a polar head group, for phosphorylcholine cytosine diphosphocholine to the exposed hydroxyl group to make phosphatidylcholine (all 3 steps occur in cytosolic face)

Phosphatidylcholine production Step 4

Flippase uses ATP energy to catalyze movement of phospholipids from the cytosolic leaflet to the exoplasmic leaflet to equalize leaflet growth and establish phospholipid asymmetry

Sphingolipid production

• Sphingosine is made in the ER beginning with the coupling of serine and palmitate via serine palmitotyltranferase on the cytosolic leaflet

• Ceramide synthase then acylates this to form N-acyl sphingosine on the cytosolic leaflet

• A polar head group or sugar group is added via a sphingolipid synthase or glucosylceramide synthase respectively

• After synthesis, sphingolipids are transported to other cellular compartments through vesicle-mediated mechanisms similar to those for the transport of proteins

Lipid transportation

Cholesterol, sphingolipids and phosphoglycerides are transported between organelles by several mechanisms

• Vesicles bud off one membrane and fuse with a target membrane to transfer lipids between membranes

• Lipids transfer directly by membrane-embedded proteins between contacting membranes

• Small, soluble lipid-transfer proteins mediate transfer