Exocytosis

Exocytosis is an energy-dependent, active transport process that cells use to expel materials like proteins and neurotransmitters. Because vital substances such as large polar molecules cannot passively cross the hydrophobic cell membrane, all cells rely on exocytosis and its reverse process, endocytosis. This mechanism releases molecules in bulk, making it a form of bulk transport. Secretory vesicles, which are membrane-bound, carry water-soluble contents to the cell surface. There, they dock and fuse at permanent, cup-shaped lipoprotein structures called porosomes, which act as secretory portals on the plasma membrane. The vesicle transiently merges with the membrane, releasing its contents into the extracellular space. In neurotransmission, synaptic vesicles typically release neurotransmitters into the synaptic cleft via exocytosis, though reverse transport through membrane proteins can also occur. Additionally, exocytosis allows cells to insert membrane proteins (like ion channels and receptors), lipids, and other components into the cell membrane by having vesicles fully fuse with and become part of the outer membrane.

The term "exocytosis" was introduced by De Duve in 1963.

In eukaryotes, exocytosis comes in two forms: Ca²⁺-triggered non-constitutive (regulated) exocytosis and non-Ca²⁺-triggered constitutive (non-regulated) exocytosis. Regulated exocytosis requires an external signal, a specific sorting signal on the vesicle, a clathrin coat, and a rise in intracellular calcium. In multicellular organisms, this process drives intercellular communication, such as synaptic transmission, hormone secretion from neuroendocrine cells, and immune cell secretion. In neurons and endocrine cells, SNARE proteins and SM-proteins catalyze fusion by forming a complex that brings the two membranes together—for example, syntaxin-1 and SNAP25 on the plasma membrane and VAMP2 on the vesicle membrane in synapses. Calcium sensors, like synaptotagmin (the major sensor in animals), may interact with the SNARE complex or with phospholipids. However, plants and unicellular eukaryotes lack synaptotagmin, and other potential sensors include EF-hand proteins (e.g., calmodulin) and C2 domain proteins (e.g., ferlins, E-synaptotagmin, Doc2b). How these sensors cooperate to achieve specific calcium-triggered kinetics remains unclear.

Constitutive exocytosis occurs in all cells, releasing extracellular matrix components or delivering newly synthesized membrane proteins to the plasma membrane after vesicle fusion. The machinery for constitutive exocytosis is less understood than that for regulated exocytosis. Two tethering complexes are involved in mammals: ELKS, a large coiled-coil protein that marks fusion "hotspots," and the octameric Exocyst complex, which localizes at both the plasma membrane and Golgi apparatus. Membrane fusion in constitutive exocytosis likely involves SNAP29 and Syntaxin19 on the plasma membrane and YKT6 or VAMP3 on the vesicle membrane.

A third type of vesicular exocytosis occurs in gram-negative bacteria. Here, the periplasm pinches off as outer membrane vesicles (OMVs), which translocate microbial biochemical signals into host cells or other microbes. This process helps the secreting microbe control its environment—facilitating host invasion, endotoxemia, or competition for nutrients. This discovery shows that exocytosis is not limited to eukaryotic cells.

Exocytosis proceeds through five steps, beginning with vesicle trafficking. For short-distance transport, such as from the Golgi apparatus to the cell surface, vesicles often use motor proteins and cytoskeletal tracks (actin or microtubules) to reach their target. Before tethering, many proteins involved in active transport would have been set for passive transport, as the Golgi apparatus does not require ATP for protein transport.