U01.01.022 Cell trafficking

Cells are like bustling cities with constant traffic flow. Proteins and lipids, essential cellular components, travel through a complex network of compartments called the endomembrane system. Here’s a breakdown of key players in this intricate trafficking system:

Golgi Apparatus: The Distribution Center

Imagine the Golgi apparatus as a central distribution center receiving goods (proteins and lipids) from the endoplasmic reticulum (ER).
It modifies these molecules through posttranslational events, like:
- Modifying N-linked sugars on asparagine residues.
- Adding O-linked sugars on serine and threonine residues.
- Attaching a critical tag, mannose-6-phosphate, to some proteins destined for lysosomes (explained later).
Once modified, the Golgi sorts and packages the molecules for their final destinations.

Endosomes: Sorting Stations for Extracellular and Internal Cargo

Endosomes act like sorting stations, processing materials from two sources:
- Extracellular materials entering the cell via endocytosis.
- Materials shipped back from the Golgi for recycling or further sorting.
Endosomes come in two flavors: early endosomes (receiving stations) and late endosomes (sorting and recycling centers).
Late endosomes decide the fate of their cargo:
- Lysosomal enzymes get a mannose-6-phosphate tag recognized by lysosomes for breakdown.
- Some materials get recycled back to the Golgi or plasma membrane for reuse.

Lysosomes: The Cellular Recycling Plant

Lysosomes are the cellular waste disposal units. They contain digestive enzymes that break down various molecules, including worn-out organelles, cellular debris, and even engulfed foreign material.
Mannose-6-phosphate on proteins acts as a recognition tag, allowing lysosomes to identify and engulf these proteins for degradation.

I-Cell Disease: A Disruption in the Trafficking System

I-cell disease (inclusion cell disease/mucolipidosis type II) is a genetic disorder affecting the Golgi apparatus.
A defect in the enzyme N-acetylglucosaminyl-1-phosphotransferase prevents the Golgi from adding the mannose-6-phosphate tag to specific proteins.
Without this tag, these proteins can’t be directed to lysosomes and get secreted outside the cell instead.
This mistargeting leads to a buildup of undegraded proteins within cells, causing various symptoms like:
- Coarse facial features
- Gingival hyperplasia (gum enlargement)
- Clouded corneas
- Joint problems
- Skeletal deformities
- High levels of lysosomal enzymes in the blood

Vesicular Trafficking Proteins: The Delivery Trucks

Vesicles are the delivery trucks that transport cargo between compartments.
COPI and COPII proteins act as coats on these vesicles, ensuring proper direction:
- COPI: Carries cargo from the Golgi back to the ER (retrograde transport).
- COPII: Transports cargo from the ER to the cis-Golgi (anterograde transport).
- It’s like a “two steps forward, one step back” process for efficient sorting and recycling.
Clathrin is another protein involved in vesicle formation, particularly for packaging cargo from the trans-Golgi to lysosomes or the plasma membrane.

Signal Recognition Particle (SRP): The Traffic Director for Protein Import

SRP acts like a traffic director, guiding newly synthesized protein chains on ribosomes to their destination in the rough endoplasmic reticulum (RER).
A dysfunctional SRP can lead to protein accumulation in the cytosol, disrupting cellular processes.

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U01.01.022 Cell trafficking

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