The Endoplasmic Reticulum

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The Endoplasmic Reticulum

• The ER consists of an extensive membrane network
  of tubes and cisternae (sac-like structures).
• The membrane encloses a space, the cisternal
  space (or internal lumen) from the cytosol.
• Parts of the ER membrane are continuous with the
  outer membrane of the nuclear envelope, and the
  cisternal space of the ER is continuous with the
  space in between the two layers of the nuclear
  envelope
• There are two types of Endoplasmic Reticulum
  Rough and Smooth.

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Rough ER functions

• Facilitate protein folding
• Only properly folded proteins are transported
  from the RER to the Golgi complex
• Transport of proteins, i.e. secretory proteins
• Insertion of ER proteins, i.e. integral proteins
• Glycosylation
• Disulfide bond formation and rearrangement

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Smooth ER Functions

• Synthesis of various lipids (e.g., for building
  membranes such as phospholipids), fatty acids and
  steroids (e.g., hormones)
• Carbohydrate metabolism. In the liver SER breaks
  down glycogen into glucose
• detoxification of the cell (enzymes in the smooth
  ER detoxify chemicals)
• Calcium storage i.e. sarcoplasmic reticulum in
  muscle cells

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Cotranslational Translocation

• The N-terminal signal sequence of the protein
  (signal sequence) is recognized by a signal
  recognition particle(SRP) while the protein is
  still being synthesized on the ribosome
• The synthesis pauses while the ribosome-protein
  complex is transferred to an SRP receptor on the
  endoplasmic reticulum (ER, which is a
  membrane-bound organelle)

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• Proteins destined for RER sorting make a signal
  sequence.
• As signal sequence elongates, it is bound by the
  signal recognition particle (SRP54) (GTP
  dependent binding).
• SRP then binds to the SRP receptor (docking
  protein) on the ER membrane.
• At the same time, ribosomes bind to the RER
  translocation channel formed by the Sec61p
  complex.
• This Sec61p complex is a major component of a
  protein-conducting channel which also includes
  the translocating chain-associating membrane
  protein or TRAM. This conducts the protein into
  the RER sac.

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• There, the nascent protein is inserted into a
  protein channel that passes through the ER
  membrane.
• The signal peptide is removed by signal peptidase
• Within the ER, the protein is first covered by a
  chaperone protein to protect it from the high
  concentration of other proteins in the ER, giving
  it time to fold correctly

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• Membrane proteins that pass through the
  membrane multiple times (called "multipass
  transmembrane proteins) have multiple start and
  stop signals.

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