Christine's Report

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    LETS LEARN MORE ABOUT ENDOPLASMIC

    RETICULUM...

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    THREE WAYS IN WHICH SINGLE PASS

    TRANSMEMBRANE PROTEINS CAN BE INSERTED

    INTO THE ER:

    (1) Simplest case: an amino-

    terminal signal peptide initiates

    translocation, just as for a solubleprotein., but an additional

    hydrophobic segment in the

    polypeptide chain stops thetransfer process before the entire

    polypeptide chain is translocated.

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    Stop transfer peptide- anchors the

    protein in the membrane after theER signal peptide is released from

    the translocator and is cleaved off.Forms a single alpha-helical

    membrane-spanning segment, with

    the amino temrinus of the protein onthe luminal side of the membrane

    and the carboxyl terminus on the

    cytosolic side.

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    (2,3) In the other 2 cases:

    The signal peptide is internal, rather

    than at the terminal end of the protein.

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    MULTIPASS TRANSMEMBRANE PROTEINS:

    the polypeptide chain passes back and forth

    repeatedly across the lipid bilayer.

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    TRANSLOCATED POLYPEPTIDE CHAINS FOLD

    AND ASSEMBLE IN THE LUMEN OF THE ROUGH

    ER:

    ER Resident proteins

    Contain an ER retention signal of four

    amino acids at their carboxyl terminus that

    is responsible for retaining the protein in

    the ER.

    Some of these proteins function as

    catalysts that help many proteins that are

    translocated into the ER to fold and

    assemble correctly.

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    EXAMPLE OF ER RESIDENT PROTEINS:

    (1) Protein disulfide isomerase

    Catalyzes the oxidation of the free

    sulfhydryl (SH) groups to form

    disulfide bonds.

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    EXAMPLES...

    (2) Binding protein (BiP)

    Chaperone protein that is structurally

    related to hsp70 proteins and, likethem, recognizes incorrectly folded

    proteins, as well as protein subunits

    that have not yet assembled into theirfinal oligomeric complexes.

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    SOME MEMBRANE PROTEINS EXCHANGE A

    CARBOXYL-TERMINAL TRANSMEMBRANE TAIL

    FOR A COVALENTLY ATTACHEDGLYCOSYLPHOSPHATIDYLINOSITOL (GPI) AFTER

    ENTRY INTO THE ER

    Glycosylphosphatidylinositol (GPI)

    Contains two fatty acids.

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    MOST MEMBRANE LIPID BILAYERS ARE

    ASSEMBLED IN THE ER

    The ER membrane produces nearly all of the

    lipids required for the elaboration of new cell

    membranes, including both phospholipids

    and cholesterol.The major phospholipid made is

    phosphatidylcholine (or lecithin), which can be

    formed in three steps from choline, two fattyacids, and glycerol phosphate.

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    2 OTHER MAJOR MEMBRANE PHOSPHOLIPIDS

    Phosphatidylethanolamine (PE) and

    Phosphatidylserine (PS) as well as the

    minor phospholipid Phosphatidylinositol(PI), are synthesized in the same

    manner as that of the lecithin.

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    Aside from producing phospholipids, the ERalso produces cholesterol and ceramide.

    Ceramide made by condensing the amino

    acid serine with a fatty acid to form the amino

    alcohol sphigosine; a second fatty acid is the

    added to form ceramide.

    transported to the GA, where it serves as

    the precursor for the synthesis of two types

    of lipids: oligosaccharide chains are added to

    form

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    glycosphingolipids, and phosphocholine head

    groups are transferred from phosphatidylcholine

    to other ceramide molecules to form

    sphingomyelin.

    Both glycosphingolipids and sphingomyelin are produced

    relatively late in the process of membrane synthesis. Because both are produced by enzymes exposed to the

    GA, they are exclusively found in the noncytosolic half of the

    lipid bilayers that contain them in contrast to the

    phospholipid synthesis which occurs in the cytosolic half of

    the lipid bilayer.

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    Recall that the plasma membrane and themembranes of the Golgi apparatus,lysosomes, and endosomes all form part of a

    membrane system that communicates withthe ER by means of transport vesicles thattransfer both proteins and lipids.

    Mitochondria, plastids and peroxisomes arenot included since they require differentmechanisms.

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    PHOSPHOLIPID EXCHANGE PROTEINS

    Also called phospholipid transfer proteins.

    Shown in vitro to have the ability to transferindividual phospholipid molecules between

    membranes. functions by "extracting" a molecule of the

    appropriate phospholipid from a membrane

    and diffusing away with the lipid buried withinits binding site.

    Recognizes only specific types of proteins.

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    PROTEIN EXCHANGE PROTEINS...

    Act to distribute phospholipids at randomamong all membranes present.

    In principle, a random exchange process can

    result in a net transport of lipids from a lipid-rich to a lipid-poor membrane, allowingphosphatidylcholine and phosphatidylserinemolecules, for example to be transferredfrom the ER where they are synthesized, to amitochondrial or peroxisomal membrane.

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    THE END!