ER Protein Retrieval

ER Protein Retrieval

• Retrieval signal is on the C-terminal of proteins: Membrane = Lys-Lys-X-X (KKXX) and Soluble = Lys-Asp-Gly-Leu (KDEL)
• The KDEL receptor shuttles back and forth between the ER and the Golgi apparatus to ensure soluble ER proteins are retained in the ER lumen
• The KDEL receptor is expected to have a higher concentration in the ER and does not have a standard ER retrieval signal

Golgi: Protein Modification

• Proteins are glycosylated to keep intermediates of protein folding soluble and prevent aggregates, signify progression of protein folding, and act as a protective coat or modulate protein function
• Complex Oligosaccharides: N-glycosylation oligosaccharide sugars are trimmed, and other sugars are added
• High Mannose Oligosaccharides: N-glycosylation oligosaccharide sugars are trimmed, and no sugars are added

Golgi Apparatus: Organization

• Proteins move from the ER (site of synthesis) to the Cis-Golgi
• In Cis-Golgi, proteins are sorted to determine which ones need to be brought back to the ER versus ones that will move on through the Golgi
• Proteins are processed and modified as they move from Cis-Golgi to Medial to Trans
• In Trans-Golgi, proteins are sorted to the plasma membrane or various intracellular organelles

Golgi Apparatus: Organization (Hypotheses)

• Hypothesis 1: Vesicle Transport Mechanism - vesicles bud from one compartment and fuse with the next one, moving non-resident proteins forward and changing the composition of each of the cisternae
• Hypothesis 2: Cisternal Maturation Mechanism - cisterna formed by transport vesicles that originate in the ER, physically move from the cis-end to the trans-end, and change their composition as they move or "mature"

ER Protein Co-Translation Translocation

• Signal peptidase cleaves signal sequence of protein being translocated
• Protein then enters lumen and folds with help of chaperones

ER Protein Post-Translation Translocation

• Some proteins do not enter ER during translation, but still need signal sequence to translocate

ER Protein Co- and Post-Translation Translocation

• ER translocons are structurally similar

ER Membrane Protein Translocation

• Membrane proteins for any secretory pathway organelle must first enter ER
• Proteins have hydrophobic stop sequences that stay in membrane
• Proteins can also be linked to the membrane with a glycosylphosphatidylinositol (GPI) anchor

Secretory Pathway: Next Steps

• Proteins in the ER have to undergo folding to form secondary, tertiary & quaternary structures, form disulfide bridges, and be modified
• Proteins in the ER have to be recognized for transport out of the ER (sorting based on signals)

ER Protein Folding

• A multitude of chaperones assist in the folding of proteins in the ER, e.g. BiP, GRP94, Calnexin (CNX) & Calreticulin (CRT)

This quiz is about the retrieval of soluble ER proteins, specifically the role of the KDEL receptor and the compartment with the highest concentration of KDEL receptors.