Protein Targeting to the Endoplasmic Reticulum, Slides of Cellular and Molecular Biology

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Protein targeting to the

Endoplasmic Reticulum

Topologically equivalent compartments in the secretory and endocytic pathways

• Network (reticulum) of membrane tubules and sheets that stretches from the nucleus to the outer periphery of the cell.
• Constantly changing shape, extending and retracting
• During cell division, the entire network breaks down into vesicles that partition into daughter cells The ER is an extensive, dynamic structure

ER structure

• Two types of ER membranes can be seen in the

electron microscope

• One appears studded with ribosomes (Rough ER) and

tends to be near the nucleus, but is still extensive.

• The other does not have ribosomes (Smooth ER) and

tends to be in the more peripheral regions of the

cell.

McGraw Hill Higher Education

RER structure

RER ribosomes are bound to the membrane because of

the nascent chains (new proteins) they are making

• The proteins are being co-translationally inserted

into the membrane (not post-translationally)

The two types of ER membranes can be separated by gradient centrifugation

Microsomes EM

Membrane bound and free polyribosomes

A signal sequence directs proteins to the ER

• The ER signal sequence : a stretch of hydrophobic amino acids.
  • N-terminal signal sequence for soluble and some membrane proteins (a.k.a signal peptide, start transfer sequence).
  • Internal sequences for many membrane proteins.
• Necessary and sufficient for ER membrane targeting
  • You only need to add this sequence to a protein and it will go to the ER membrane
• Leads to co-translational translocation across ER membrane.
• N-terminal start transfer sequences are usually cleaved by signal peptidase, so the sequence is not found in the mature protein
• The protein folds in the lumen with the help of chaperones and other molecules
• This protein is now either soluble in the lumen of the ER, or associated with the ER membrane.

Proteins destined for the ER are transported by a

cotranslational transmembrane mechanism

How is the ER targeting signal recognized?

• Signal sequence emerges from ribosome
• Associates with the Signal Recognition Particle (SRP)