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Proteins targeted to organelles, such as the endosome, cellular membranes, or for extracellular

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secretion, must be modified.

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The modification is necessary for the correct delivery of the protein to its final cellular

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location.

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The modification occurs when specific sugar molecules are added to a core oligosaccharide

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that is attached to the protein.

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These sugar complexes are the signal often required to direct the protein to its final destination.

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One example of this is mannose 6-phosphate.

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These sugar side chain modifications occur within the Golgi apparatus.

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We focus here on the delivery of a hydrolase enzyme to the endosome.

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Hydrolases are enzymes that degrade other molecules.

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The endosome is an organelle that contains molecules to be degraded.

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Other key components include the M6P receptor protein.

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So let's follow a hydrolase from the endoplasmic reticulum, or ER,

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where it is synthesized, to the endosome.

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First, the hydrolase is delivered from the ER to the Golgi apparatus via a vesicle.

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While it is being transferred through the ER and cis cisterna of the Golgi apparatus,

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the modification of the sugar core oligosaccharide begins.

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The term for this process is glycosylation.

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Here, we show two steps involved in the production of the mannose 6-phosphate signal.

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In humans, defects in Golgi glycosylation can lead to specific diseases.

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Once the hydrolase reaches the trans-Golgi cisternae, the mannose 6-phosphate signal has been completed.

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Only proteins destined for the endosome have the mannose 6-phosphate signal.

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Once modified, the hydrolase is bound to the mannose 6 receptor protein through the mannose 6 phosphate molecule.

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The receptor has a domain that extends through the transgolgi membrane.

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Through the interaction with this receptor, the hydrolase is associated with the transgolgi membrane.

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Next, a vesicle containing the hydrolase buds off from the transgolgi and moves to the endosome.

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Endosomes eventually mature into lysosomes.

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Other proteins have different sugar side chains and they are delivered to other cellular locations,

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or to the cell membrane where it is embedded or secreted.

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The vesicle docks and fuses with the endosome.

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At this point, the hydrolase is released.

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Soon after, the phosphate portion of the mannose 6-phosphate signal is removed.

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Before it can go on to degrade other molecules,

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the hydrolase will undergo a final modification to become an active enzyme.

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The M6P receptors are then recycled back to the Golgi.

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The sugar side chain signal added by glycosylation in the Golgi apparatus

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is a key element of the process that directs certain proteins to their proper cellular locations.