Protein Modification (Golgi) -- Movie Narrative

Proteins targeted to organelles such as the endosome, cellular membranes, or for extracellular secretion, must be modified. The modification is necessary for the correct delivery of the protein to its final cellular location.

The modification occurs when specific sugar molecules are added to a core oligosaccharide that is attached to the protein. These sugar complexes are the signal often required to direct the protein to its final destination. One example of this, is mannose 6-phosphate.

These sugar side chains modifications occur within the Golgi apparatus.

We focus here on the delivery of a hydrolase enzyme to the endosome. Hydrolases are enzymes that degrade other molecules. The endosome is an organelle that contains molecules to be degraded. Other key components include the M6P receptor protein.

So let's follow a hydrolase from the endoplasmic reticulum, or ER, where it is synthesized, to the endosome.

First, the hydrolase is delivered from the ER to the Golgi Apparatus via a vesicle. While it is being transfered through the ER and cis-cisterna of the Golgi apparatus, modification of the sugar core oligosaccharide begins. The term for this process is glycosylation.

Here we show two steps involved in the production of the mannose 6-phosphate signal. In humans, defects in Golgi glycosylation can lead to specific diseases. Once the hydrolase reaches the trans-golgi cisternae the mannose 6-phosphate signal has been completed. Only proteins destined for the endosome have the mannose 6-phosphate signal.

Once modified the hydrolase is bound to the mannose-6 receptor protein through the mannose-6-phosphate molecule. The receptor has a domain that extends through the trans-golgi membrane. Through the interaction with the receptor the hydrolase is associated with the trans-golgi membrane.

Next, a vesicle containing the hydrolase buds off from the trans-Golgi and moves to the endosome. Endosomes eventually mature into Lysosomes. Other proteins have different sugar side chains and they are delivered to other cellular locations or to the cell membrane where it is embedded or secreted.

The vesicle docks and fuses with the endosome. At this point, the hydrolase is released. Soon after, the phosphate portion of the mannose 6-phosphate signal is removed. Before it can go on to degrade other molecules, the hydrolase will undergo a final modification to become an active enzyme. The M6P receptors are then recycled back to the Golgi.

The sugar side chain signal, added by glycosylation in the Golgi Apparatus, is a key element of the process that directs certain proteins to their proper cellular locations.