Molecular Genetics

The absence of a trafficking signal relegates a protein to a default path.

Facts

• In human I-cell disease, a Mendelianly inherited condition, lysosomal enzymes are found in the serum.
• Lysosomal enzymes in unaffected individuals are glycoproteins whose sugar moieties contain phosphoryl mannose. The serum enzymes lack phosphoryl groups on their mannose residues.
• Lysosomal enzymes in unaffected and affected indivduals are synthesized on the rough endoplasmic reticulum (RER) and enter the RER-->SER-->Golgi pathway.

Interpretations

• The I-cell disease defect is a failure to phosphorylate mannose residues on polypeptides normally destined for the lysosome.
• Phosphoryl mannose is a signal for transfer of proteins to lysosomes.
• The absence of a signal, such as phosphoryl mannose, relegates a protein to a default path--in this case, secretion from the cell.

Further information

• Other proteins entering the RER-->SER-->Golgi pathway are also removed to cellular destinations because they contain specific signals.

This is page 2544 of Molecular Genetics by Ulrich Melcher, © 1997, 1999