Question

1. Trace the route of a protein from synthesis to import into a lysosome. What signals are necessary? Trace the route of a protein from synthesis to import into a peroxisome. What signals are necessary?

Answer 1

• After translation process in ribosomes, the polypeptide chain generated undergoes several post-translational modifications and changes and are translocated to other area of the cell or secreted out of the cell, by the process of protein trafficking.
• The proteins are recognized by a short signal sequence (6-12 amino acid sequence) present at the N-terminus, and are targeted to specific organelles, including endoplasmic reticulum, Golgi apparatus, lysosome, by protein targeting.
• While some proteins are not associated with the signal peptide.

1. Lysosome targetting of proteins:

• Lysosome targeting of protein occurs in Cis- Golgi network (CGN).
• N-Acetyl glucosamine (NAG) phosphorylases, first binds to Mannose residues.
• The NAG part is then removed, and Mannose -6- phosphate (M-6-P) is retained on the N-linked oligosaccharide.
• Mannose phosphorylation of proteins is the indication of protein transportation to lysosome.
• Phosphorylated protein is recognized by M-6-P receptor on trans- Golgi network (TGN), and these proteins are directed to lysosome. Signal patch on lysosome recognizes the M-6-P related protein.

· membrane. Further, sub-compartment localization occurs as needed.

2. Peroxisome protein targeting:

• These peptides are usually synthesized in free ribosomes.
• Thus, the proteins can be directly transferred to the peroxisomes.
• For targeting to peroxisome, proteins are associated with signal called PTS or Peroxisomal targeting signal.
• The main matrix targeting sequences are C-terminal sequences- as S-A/C: K-R/H: L-A.
• This includes a tripeptide SKL (Serine-Lysine-Leucine), like PTS-1.
• Another matrix protein, is the N-terminal signal (consensus- R-K: L-V/I: 5 amino acids : H-Q: L-A/F).
• If either of the signals are absent, some proteins may be carried to peroxisomes with PTS-1 proteins, by a process termed as piggy back technique.
• Peroxisomal membrane proteins (PMP) contain signal called mPTS. They may be directly translocated through cytosol or targeted via endoplasmic reticulum