Membrane Trafficking Overview and Pathways

Study Notes

Membrane trafficking is a crucial cellular process for maintaining cell viability. It transports nutrients and other solutes to all parts of the cellular system.
It is a complex and highly regulated system analogous to a parcel sorting office, ensuring the correct cargo is delivered to its designated location within or outside the cell.
This process encompasses a variety of mechanisms for moving cargo, typically proteins, pathogens, and other macromolecules using membrane-bound transport vesicles.
Transport can occur within organelles of the same cell or across the cell membrane between the cell and the extracellular environment.

Membrane trafficking is categorized into two fundamental pathways based on the direction of movement:
- Endocytic pathway/Endocytosis—involves movement of cargo into the cell from the plasma membrane and is crucial for nutrient uptake (e.g., vitamins, cholesterol, iron).
- Secretory pathway/Exocytosis—involves movement of cargo, like newly synthesized proteins, lipids, or carbohydrates, to the cell membrane or out of the cell, often following the biosynthetic-secretory pathway.

Protein trafficking is vital as proteins must be delivered to the correct location.
Transport vesicles facilitate membrane trafficking.
Mechanisms of protein trafficking can be categorized into two types:
- Vesicle-mediated trafficking: Involves proteins manufactured in ER ribosomes.
- Non-vesicle-mediated trafficking: Involves proteins manufactured in free or cytosolic ribosomes.
Proteins synthesized on free ribosomes in the cytosol may either remain in the cytosol or be transported to the nucleus, mitochondria, chloroplasts, or peroxisomes.
Proteins synthesized on membrane-bound ribosomes are translocated into the ER while their translation occurs.
These proteins are then either retained within the ER, or transported to the Golgi apparatus, then to lysosomes. Alternatively transported directly to the plasma membrane or to the extracellular environment via secretory vesicles.

In the secretory pathway, proteins move from the rough ER to the Golgi, then to secretory vesicles, then to the cell exterior.
Proteins destined for secretion or incorporation into the ER, Golgi apparatus, lysosomes, or plasma membrane are initially targeted to the ER.
The entry of proteins into the ER marks a major sorting point in eukaryotic cells.

The Golgi apparatus (Golgi complex) is composed of flattened membrane-enclosed sacs, receiving proteins from the ER, processing them, and sorting them to their final destinations.
The Golgi apparatus is divided into regions (cis Golgi network, medial Golgi stack, and trans Golgi network), each with specific protein modifications occurring within them.
Proteins from the ER reach the cis Golgi network, then the medial and then the trans Golgi; proteins are then carried to their final destination.
Proteins destined to remain in the ER are marked with the KDEL sequence, enabling retrieval back to the ER.

Vesicle transport is essential for transporting proteins and lipids between the three principal organelles of the secretory pathway—the endoplasmic reticulum (ER), Golgi apparatus, and plasma membrane.
Vesicles are either small vesicles or larger vesicle-tubule elements moving along microtubules between membranes. These vesicles originate from ER export sites (ERES), evolving into vesicular tubular carriers (VTCs) before reaching the Golgi apparatus.
Vesicle transport requires a precise mechanism.
- Cargo recognition by the correct target membrane to ensure delivery to the correct organelle.
- Fusion of the vesicle and target membranes allowing content release to the targeted organelle.
- Specific protein machinery, including v-SNAREs (vesicle-SNAREs) and t-SNAREs (target-SNAREs) and tethering proteins, is involved in vesicle fusion to ensure membrane fusion.

Most transport vesicles are coated with proteins, hence called coated vesicles.
These coated vesicles are categorized into COP-coated vesicles, COPI, and COPII (indicating coat protein), and clathrin-coated vesicles.

Membrane trafficking is a complex cellular process ensuring the efficient movement of proteins, lipids, and other molecules within and out of the cell.
Various mechanisms are used, including endocytosis and exocytosis mediated through transport vesicles and the functions of the ER, Golgi, and other organelles.
Specific protein machinery is critical in these transport steps.