Secretion
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
Secretion in bacterial species means the transport or translocation of effector molecules. For example, proteins, enzymes or toxins move from across the interior of a bacterial cell to its exterior. Secretion is a very important mechanism in bacterial functioning and operation in their natural surrounding environment for adaptation and survival.
In eukaryotic cells
Mechanism
s, including human cells, have a highly evolved process of secretion. Proteins targeted for the outside are synthesized by ribosomes docked to the rough endoplasmic reticulum. As they are synthesized, these proteins translocate into the ER lumen, where they are glycosylated and where molecular chaperones aid protein folding. Misfolded proteins are usually identified here and retrotranslocated by ER-associated degradation to the cytosol, where they are degraded by a proteasome. The vesicles containing the properly folded proteins then enter the Golgi apparatus.In the Golgi apparatus, the glycosylation of the proteins is modified and further post-translational modifications, including cleavage and functionalization, may occur. The proteins are then moved into secretory vesicles which travel along the cytoskeleton to the edge of the cell. More modification can occur in the secretory vesicles.
Eventually, there is vesicle fusion with the cell membrane at porosomes, by a process called exocytosis, dumping its contents out of the cell's environment.
Strict biochemical control is maintained over this sequence by usage of a pH gradient: the pH of the cytosol is 7.4, the ER's pH is 7.0, and the cis-golgi has a pH of 6.5. Secretory vesicles have pHs ranging between 5.0 and 6.0; some secretory vesicles evolve into lysosomes, which have a pH of 4.8.
Nonclassical secretion
There are many proteins like FGF1, FGF2, interleukin-1 etc. which do not have a signal sequence. They do not use the classical ER-Golgi pathway. These are secreted through various nonclassical pathways.At least four nonclassical protein secretion pathways have been described. They include:
- direct protein translocation across the plasma membrane likely through membrane transport proteins
- blebbing
- lysosomal secretion
- release via exosomes derived from multivesicular bodies
In human tissues
Many human cell types have the ability to be secretory cells. They have a well-developed endoplasmic reticulum, and Golgi apparatus to fulfill this function. Tissues that produce secretions include the gastrointestinal tract, which secretes digestive enzymes and gastric acid, the lungs, which secrete surfactants, and sebaceous glands, which secrete sebum to lubricate the skin and hair. Meibomian glands in the eyelid secrete meibum to lubricate and protect the eye.In gram-negative bacteria
Secretion is not unique to eukaryotes – it is also present in bacteria and archaea as well. ATP binding cassette type transporters are common to the three domains of life. Some secreted proteins are translocated across the cytoplasmic membrane by the SecYEG translocon, one of two translocation systems, which requires the presence of an N-terminal signal peptide on the secreted protein. Others are translocated across the cytoplasmic membrane by the twin-arginine translocation pathway. Gram-negative bacteria have two membranes, thus making secretion topologically more complex. There are at least six specialized secretion systems in Gram-negative bacteria.Type I secretion system (T1SS or TOSS)
Type I secretion is a chaperone dependent secretion system employing the Hly and Tol gene clusters. The process begins as a leader sequence on the protein to be secreted is recognized by HlyA and binds HlyB on the membrane. This signal sequence is extremely specific for the ABC transporter. The HlyAB complex stimulates HlyD which begins to uncoil and reaches the outer membrane where TolC recognizes a terminal molecule or signal on HlyD. HlyD recruits TolC to the inner membrane and HlyA is excreted outside of the outer membrane via a long-tunnel protein channel.Type I secretion system transports various molecules, from ions, drugs, to proteins of various sizes. The molecules secreted vary in size from the small Escherichia coli peptide colicin V, to the Pseudomonas fluorescens cell adhesion protein LapA of 520 kDa. The best characterized are the RTX toxins and the lipases. Type I secretion is also involved in export of non-proteinaceous substrates like cyclic β-glucans and polysaccharides.
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Type II secretion system (T2SS)
Proteins secreted through the type II system, or main terminal branch of the general secretory pathway, depend on the Sec or Tat system for initial transport into the periplasm. Once there, they pass through the outer membrane via a multimeric complex of pore forming secretin proteins. In addition to the secretin protein, 10–15 other inner and outer membrane proteins compose the full secretion apparatus, many with as yet unknown function. Gram-negative type IV pili use a modified version of the type II system for their biogenesis, and in some cases certain proteins are shared between a pilus complex and type II system within a single bacterial species.Type III secretion system (T3SS or TTSS)
It is homologous to the basal body in bacterial flagella. It is like a molecular syringe through which a bacterium can inject proteins into eukaryotic cells. The low Ca2+ concentration in the cytosol opens the gate that regulates T3SS. One such mechanism to detect low calcium concentration has been illustrated by the lcrV antigen utilized by Yersinia pestis, which is used to detect low calcium concentrations and elicits T3SS attachment. The Hrp system in plant pathogens inject harpins and pathogen effector proteins through similar mechanisms into plants. This secretion system was first discovered in Yersinia pestis and showed that toxins could be injected directly from the bacterial cytoplasm into the cytoplasm of its host's cells rather than simply be secreted into the extracellular medium.Type IV secretion system (T4SS or TFSS)
It is homologous to conjugation machinery of bacteria, the conjugative pili. It is capable of transporting both DNA and proteins. It was discovered in Agrobacterium tumefaciens, which uses this system to introduce the T-DNA portion of the Ti plasmid into the plant host, which in turn causes the affected area to develop into a crown gall. Helicobacter pylori uses a type IV secretion system to deliver CagA into gastric epithelial cells, which is associated with gastric carcinogenesis. Bordetella pertussis, the causative agent of whooping cough, secretes the pertussis toxin partly through the type IV system. Legionella pneumophila, the causing agent of legionellosis utilizes a type IVB secretion system, known as the icm/dot system, to translocate numerous effector proteins into its eukaryotic host. The prototypic Type IVA secretion system is the VirB complex of Agrobacterium tumefaciens.Protein members of this family are components of the type IV secretion system. They mediate intracellular transfer of macromolecules via a mechanism ancestrally related to that of bacterial conjugation machineries.