Endoplasmic Reticulum (Block 1)

What is an important family of enzymes that the smooth ER uses to detoxify?

cytochrome p450s

Where are newly synthesized phospholipids inserted?

Into leaflet of bilayer that faces the cytosol

After a protein is completely translated what happens and where does it go?

It disengages from the ribosome. The protein is completely folded and floating around in the cytoplasm. Where it goes is dependent of whether it has a targeting signal or not.

What is scrambalase and what does it do?

It is a membrane-bound phospholipid translocator required to transfer lipid molecules from the cytosolic half to the lumenal half so that the membrane grows as a bilayer.

Differentiate between scramblase, flippase, and floppase.

- A scramblase moves phospholipids from one leaflet of the bilayer to the other in both directions - A flippase only moves phospholipids from the extracellular leaflet of the bilayer to the cytoplasmic leaflet - A floppase only moves phospholipids from the cytoplasmic leaflet to the extracellular leaflet

What are the characteristics of ER signal sequences?

-All have 8 or more non-polar(hydrophobic) amino acids at their center -usually at amino terminus (but not always) -usually cleaved in ER lumen by signal peptidase (but not always)

What is lipid biosynthesis?

-The smooth ER membrane synthesizes nearly all of the major classes of lipids, including cholesterol. (Exception: Cardiolipin which is synthesized in the Mitochondria).

What are the 2 main functions of the smooth ER?

1) Lipid Biosynthesis 2) Detoxification Reactions

As a protein chain enters the ER lumen, in what ways is it modified?

1) N-terminal signal peptides are usually cleaved by signal peptidase 2) Most proteins in ER lumen receive N-linked (asparagine, N) glycosylation which aids in folding 3) Third possible protein modification in ER lumen-formation of disulfide bonds. Free sulfhydrals (SH) on cysteine residues are oxidized in ER lumen to form disulphide (S-S) bonds which aids in folding. 4) Some membrane proteins lose their transmembrane domain and gain a GPI anchor 5) Another modification-protein folds (aided by chaperones of the ER lumen such as BIP, which is homologous to cytosolic HSP70)

What are the ways a lipid in a cell reaches other cellular membranes from the smooth ER?

1) diffuse to the rough ER which is continuous to the smooth ER (diffusion to continuous organelle) 2) by vesicles that bud off and are moved to other membranes with which they fuse (vesicular traffic) 3) by transfer proteins (take lipids to organelles like mitochondria that don't receive vesicle traffic from the ER)

What are the 2 main types of chaperones?

1) hsp70 (heat shock protein 70 family) includes hsp70 in cytoplasm and BiP in ER lumen-bind to hydrophobic domains that are only present in unfolded proteins 2) GroEL family

Why can scrambalase equilibrate the different phospholipids between the two monolayers?

Because scramblase is not specific for particular phospholipid head groups.

Why is smooth ER common in cells engaged in steroid synthesis?

Because steroid hormones are synthesized from cholesterol and because smooth ER contains some of the membrane-bound enzymes required for this process.

What is the ER?

Membrane-bounded compartment in the cytoplasm, where lipids, and cholesterol are synthesized and membrane-bound proteins and secretory proteins are made.

What are ER tubules held in place by?

Microtubules

What causes cystic fibrosis?

Mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene causing inability to transport Cl ions in/out cells. There is a mutant protein which misfolds, which gets the protein degraded even though it would still have the ability to transport Cl ions.

Where are most of the lipids in a cell synthesized and what are the lipids synthesized?

Phospholipids and cholesterol and are synthesized on smooth ER.

What is Post-translational protein targeting?

Proteins in the cytosol, mitochondria, peroxisomes, and the nuclear interior are translated on ribosomes free in the cytosol and then moved to their final destination based on if they contain a targeting signal and what type it is.

Where are ribosomes found and what is the difference in where they are found?

Ribosomes in the process of translating messages are found in two places inside the cell, 1) free in the cytoplasm and 2) bound to the rough ER ***All ribosomes are the same, the difference between ribosomes in the two locations is the type of message they are translating

What is the difference between scramblase and flippase?

Scramblase only acts in the ER membrane and flippase only acts at the plasma membrane.

The more cholesterol a cell needs, the more _____ it has.

Smooth ER

What is rough ER continuous with?

Smooth ER

What is co-translational protein targeting?

Synthesized by ribosomes bound to the ER membrane. The force of adding amino acids to the chain pushes the chain across the ER membrane

What happens when large amounts of certain compounds, such as the drug phenobarbital enter the system?

The smooth ER in the liver doubles in surface area in a couple of days. This is due to the rapid synthesis of the detoxification enzymes, and the cell needs more membrane to put them in. ***proliferation of smooth ER when needed, like the proliferation of peroxisomes when needed

What happens to ER misfolded proteins?

They are ubiquitinized and sent to cytosol to be degraded by the proteasome.

What is the process of phospholipid distribution in the plasma membrane?

Using ATP hydrolysis, a head-group specific "flippase" in the plasma membrane flips phosphatidylserine and phosphatidyl-ethanolamine from the extracellular to the cytosolic leaflet, creating the lipid bilayer.

What causes the the protein to be translated on the ER?

When you start translating a message and it has an ER signal sequence, there is an SRP, signal recognition particle which takes it to the ER membrane.