Vesicular transport, endocytosis and exocytosis

Vesicular transport involves the movement of molecules enclosed by membranes.

Vesicles form when a portion of the membrane encloses molecules, particles, or even entire cells. These vesicles can then fuse with other membranes to release their contents.

• Endocytosis is the process of bringing substances into the cell.
• Exocytosis is the process by which the cell releases substances to the outside.

These processes are interconnected to help maintain a stable membrane surface area.

Types of Endocytosis

Cells use endocytosis to internalize various extracellular materials, including nutrients, ligands bound to receptors, immune signaling molecules, pathogens, and toxins.

Endocytosis types

Phagocytosis

Specialized for the uptake of large, solid particles such as apoptotic cells, bacteria, viruses, and foreign bodies.

The plasma membrane surrounds the object, enclosing it in a large vesicle called a phagosome.

The contents are then degraded in lysosomes.

Pinocytosis

Involves the uptake of extracellular fluid and dissolved substances.

A membrane protrusion forms and pinches off into a fluid-filled vesicle.

The vesicle enters the cytosol and fuses with endosomes or lysosomes for further processing.

Receptor-Mediated Endocytosis

Allows specific uptake of molecules via surface receptors.

The plasma membrane invaginates, forming a coated pit, which pinches off into a coated vesicle.

This process is mediated by several proteins:

• Clathrin - forms a mesh-like coat around the vesicle.
• Caveolin - creates invaginations known as caveolae.

Examples of substances taken up this way include folic acid, LDL lipoproteins, transferrin, and protein hormones like EGF.

Adaptor protein AP2 recognizes phospholipids and receptor proteins with specific sequences, initiating coated pit formation.

Clathrin binds to AP2, supporting membrane invagination.

Dynamin, a G-protein, helps pinch off the coated vesicle from the membrane.

After internalization, the vesicle fuses with endosomes, and clathrin, AP2, and dynamin are released.

Exocytosis

Exocytosis is used by cells to secrete substances into the extracellular environment. For example:

• Hepatocytes - plasma proteins
• Plasma cells - antibodies
• Glandular cells - hormones
• Neurons - neurotransmitters

Key proteins in exocytosis include:

SNARE proteins, which mediate vesicle docking and membrane fusion:

• Synaptobrevin (v-SNARE) from vesicles binds to syntaxin and SNAP-25 (t-SNAREs) on the target membrane.

Rab 3, a G-protein, and synaptotagmin, which binds Ca²⁺.

• Upon Ca²⁺ binding, synaptotagmin undergoes a conformational change, triggering SNARE complex formation and membrane fusion.

Pathobiochemistry

Some bacteria interfere with vesicular transport, especially at synapses:

Clostridium tetani and Clostridium botulinum produce toxins that block neurotransmitter release, leading to tetanus and botulism. Their toxins are zinc proteases that cleave SNARE proteins, preventing synaptic transmission.

Recombinant botulotoxin is used in medicine, such as for wrinkle smoothing treatments.

Sources

MATOUŠ, Bohuslav, et al. Základy lékařské chemie a biochemie. 1. vydání. Praha : Galén, 2010. 540 s.