The cell. 5. Vesicular traffic.
|« Golgi complex||Endocytosis »|
Exocytosis is a process by which vesicles fuse with the plasma membrane.
From the trans domain of the Golgi complex to the plasma membrane, vesicles can take two pathways: constitutive and regulated exocytosis.
Constitutive exocytosis is present in every cell, it is the default pathway. Molecules are carried by vesicles toward plasma membrane and extracellular matrix.
Regulated exocytosis takes place in the secretory cells. In this exocytic pathway, vesicles are not immediately fused with plasma membrane, but they do it after a signal arrives. Furthermore, there are specific regions of the plasma membrane where these vesicles are docked more frequently.
There are also other vesicles, not coming from the Golgi complex, that fuse with plasma membrane.
From the TGN (trans Golgi network) of the Golgi complex, vesicles are originated and directed to different targets: previous Golgi cisternae/endoplasmic reticulum, endosomes, and plasma membrane. In this page we will focus on the path to the plasma membrane, whereas we will deal with the path to the endosomes in the pages dedicated to this organelle and to the lysosome.
Exocytosis is the fusion of vesicles with the plasma membrane. Vesicles mainly come from the Golgi complex, but also from endosomes (see below). In the Golgi complex, vesicles are formed in the TGN and are moved to the plasma membrana, where they get fused. There are two types of exocytosis: constitutive and regulated. Constitutive exocytosis is present in almost every cell and carries molecules needed by plasma membrane and extracellular matrix. It is the default exocytic pathway. It is a continuous traffic where the amount of vesicles depends on the physiological state of the cell. Regulated exocytosis is present in cells specialized in secretion, such as endocrine cells, neurons, intestine epithelial cells, glandular cells, and others. For example, by regulated exocytosis, molecules are release to the intestine lumen for digestion, and other cells release molecules to the extracellular matrix to modulate tissue physiology, either being located close or quite far in body, where they arrive through blood vessels like hormones. Vesicles of regulated exocytosis do not fuse spontaneously with cell membrane, but after the arriving of a signal, which is usually an increase on the cytoplasmic calcium concentratrion. Furthermore, ATP and GTP are needed as energy sources.
From TGN of the Golgi complex, vesicles depart toward different cell compartments. Two pathways end at the plasma membrane. One is known as constitutive exocytosis, which is present in almost every cell, whereas the other is known as regulated exocytosis, which is present in secretory cells. Regulated exocytosis need a signal for the vesicles to fuse to plasma membrane. Other pathway from the TGN directs vesicles toward endosome/multivesicular bodies, vesicles formation is mediated by clathrin coats. Another pathway is toward previous cisternae of the Golgi complex, mediated by COPI coats.
In regulated exocytosis, vesicles are stored in the cytoplasm and are moved to specific plasma membrane regions after the cell receives a signal. So, it is a regulated process not only temporally but also spatially. Neurons show a good example of regulated exocytosis. In these cells, some vesicles are formed around the nucleus, in the soma, and are moved to the presynaptic terminal, which can be several centimeters away from the soma. These vesicles fuse with the presynaptic membrane after the arriving of an action potential. Other polarized cells are the enterocytes of the intestine epithelium, which have an apical domain facing the lumen of the intestine and a basolateral domain. It would be a catastrophe if vesicles loaded with digestive enzymes are released to the basolateral domains because the surrounding tissue would be digested. These vesicles are moved to the correct domain of the membrane, the apical one, by microtubules of the cytoskeleton, helped by kinesin motor proteins.
Constitutive and regulated exocytic vesicles transport different types of molecules. Thus, the TGN of the Golgi complex must separate both types of cargoes. It is thought that molecules without a specific signal or with saccharides, as the membrane glycoproteins, are packaged in the constitutive exocytic vesicles. It is a kind of default pathway. Molecules which are part of the membrane of these vesicles will form part of the plasma membrane, whereas those transported inside the vesicle are released to the extracellular matrix, where they develop their functions.
At the beginning, regulated exocytic vesicles are small and, once in the cytosol, start to fuse with each other, resulting in larger vesicles. They remain in the cytosol until a signal arrives and then are moved toward the plasma membrane and fused with it. How molecules for regulated exocytosis are selected in the TGN? It has been suggested that they spontaneously form large molecular aggregates. In these aggregates, there are also enzymes that process the molecules which are released as physiological signals. This processing is because many molecules are included in vesicles as non active precursors, but are released as active molecules.
The kiss and run model of exocytosis proposes that the vesicle content is released to the extracellular space without the need of a permanent fusion of the vesicle and the plasma membranes. Instead, a partial fusion produces a transient pore that allows the molecules to diffuse from the vesicle toward the extracellular space.
Exocytosis involves the fusion of vesicle and plasma membranes, and vesicle membrane molecules become part of the plasma membrane. However, some electron microscopy images suggest other exocytosis mechanism, which has been named "kiss and run". This model proposes that vesicle does not end as part of the plasma membrane because the fusion process is transient. So that there is an initial fusion between vesicle and plasma membrane that affects to a small area of both membranes. In this area, a small pore is opened allowing the communication between the interior of the vesicle and the extracellular space, through which soluble molecules are released by diffusion. The pore is transient and gets closed after a while, vesicle and plasma membranes are sealed again, and vesicle is free and empty in the cytosol. The kiss and run mechanism is thought to occur in many cell types, particularly in synaptic terminals of neurons and in chromaffin cells.
Some vesicles bud from the early endosomes and are moved toward the plasma membrane. The purpose of this exocytic pathway is recycling.
In the presynaptic terminals, there is a local cycle of formation, loading, and exocytosis of vesicles. Vesicles are formed in the plasma membrane, near the presynaptic density. Once free inside the presynaptic terminal, vesicles get loaded with neurotransmitters. After the arriving of an action potential at the presynaptic terminal, vesicles are fused with the presynaptic density membrane and release the neurotransmitter to the synaptic cleft.
Not all vesicles that get fused with the plasma membrane are released by the Golgi complex. Early endosomes are organelles that receive endocytic vesicles (vesicles formed in the plasma membrane). After the fusion of these vesicles with the endosome, part of the vesicle content, particularly membrane proteins and lipids, is recycled back to the plasma membrane by budding of vesicles from the endosome itself. Another example of exocytic vesicles not coming from the Golgi complex are the vesicles of synaptic terminals of the nervous system. Axonal synapsis are usually far away from the Golgi complex, which is located in the neuronal soma. Neurotransmitter release can not wait to a long and slow transport of neurotransmitters from the soma to the end of the axonal branch, because the nerve communication would be slow and inefficient. To avoid that, there is a local exocytosis mechanism in the synaptic terminals. It starts with vesicle formation in the cell membrane near the synaptic density. After vesicles are released from the plasma membrane are loaded with neurotransmitters that cross the membrane vesicle by transporters located in the vesicle membrane itself. Once loaded, vesicles are moved close to the presynaptic density, where they are ready to fuse with the plasma membrane (exocytosis) after the action potential arrives. In this way, there is a continuous production of vesicles, loading and exocytosis (release of neurotransmitters) in the synaptic terminal, so it is much more efficient.
Dikeakos JD, Reudelhuber TL. 2007. Sending proteins to dense core secretory granules: still a lot of sort out. Journal of cell biology. 177: 191-196.
|« Golgi complex||Endocytosis »|
Updated: 2018-01-28. 15:16
Atlas of Plant and Animal Histology
Dep. of Functional Biology and Health Sciences.
Faculty of Biology.
University of Vigo