Cell adhesion
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Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as
General mechanism
CAMs are classified into four major families:
In multicellular organisms, bindings between CAMs allow cells to adhere to one another and creates structures called
- Anchoring junctions (hemidesmosomes), which maintain cells together and strengthens contact between cells.
- Occluding junctions (tight junctions), which seal gaps between cells through cell–cell contact, making an impermeable barrier for diffusion
- Channel-forming junctions (gap junctions), which links cytoplasm of adjacent cells allowing transport of molecules to occur between cells
- Signal-relaying junctions, which can be synapses in the nervous system
Alternatively, cell junctions can be categorised into two main types according to what interacts with the cell: cell–cell junctions, mainly mediated by cadherins, and cell–matrix junctions, mainly mediated by integrins.
Cell–cell junctions
Cell–cell junctions can occur in different forms. In anchoring junctions between cells such as adherens junctions and desmosomes, the main CAMs present are the cadherins. This family of CAMs are membrane proteins that mediate cell–cell adhesion through its extracellular domains and require extracellular Ca2+ ions to function correctly.[2] Cadherins forms homophilic attachment between themselves, which results in cells of a similar type sticking together and can lead to selective cell adhesion, allowing vertebrate cells to assemble into organised tissues.[1] Cadherins are essential for cell–cell adhesion and cell signalling in multicellular animals and can be separated into two types: classical cadherins and non-classical cadherins.[2]
Adherens junctions
Adherens junctions mainly function to maintain the shape of tissues and to hold cells together. In adherens junctions,
Desmosomes
Desmosomes are structurally similar to adherens junctions but composed of different components. Instead of classical cadherins, non-classical cadherins such as
Tight junctions
Tight junctions are normally present in
Gap junctions
Gap junctions are composed of channels called
Adhesion mediated by selectins
Selectins are a family of specialised CAMs involved in transient cell–cell adhesion occurring in the circulatory system. They mainly mediate the movement of
Adhesion mediated by members of the immunoglobulin superfamily
The immunoglobulin superfamily (IgSF) is one of the largest superfamily of proteins in the body and it contains many diverse CAMs involved in different functions. These transmembrane proteins have one or more
Cell–matrix junctions
Cells create extracellular matrix by releasing molecules into its surrounding extracellular space. Cells have specific CAMs that will bind to molecules in the extracellular matrix and link the matrix to the intracellular cytoskeleton.[1] Extracellular matrix can act as a support when organising cells into tissues and can also be involved in cell signalling by activating intracellular pathways when bound to the CAMs.[2]
Cell–matrix junctions are mainly mediated by integrins, which also clusters like cadherins to form firm adhesions. Integrins are transmembrane heterodimers formed by different α and β subunits, both subunits with different domain structures.
Hemidesmosomes
In hemidesmosomes, integrins attach to extracellular matrix proteins called
Focal adhesions
In focal adhesions, integrins attach
Other organisms
Eukaryotes
Plants cells adhere closely to each other and are connected through
Pathogenic
Prokaryotes
Adhesins can recognise a variety of ligands present on the host cell surfaces and also components in the extracellular matrix. These molecules also control host specificity and regulate tropism (tissue- or cell-specific interactions) through their interaction with their ligands.[34]
Viruses
Clinical implications
Dysfunction of cell adhesion occurs during cancer metastasis. Loss of cell–cell adhesion in metastatic tumour cells allows them to escape their site of origin and spread through the circulatory system.[5] One example of CAMs deregulated in cancer are cadherins, which are inactivated either by genetic mutations or by other oncogenic signalling molecules, allowing cancer cells to migrate and be more invasive.[6] Other CAMs, like selectins and integrins, can facilitate metastasis by mediating cell–cell interactions between migrating metastatic tumour cells in the circulatory system with endothelial cells of other distant tissues.[37] Due to the link between CAMs and cancer metastasis, these molecules could be potential therapeutic targets for cancer treatment.
There are also other human genetic diseases caused by an inability to express specific adhesion molecules. An example is leukocyte adhesion deficiency-I (LAD-I), where expression of the β2 integrin subunit is reduced or lost.[38] This leads to reduced expression of β2 integrin heterodimers, which are required for leukocytes to firmly attach to the endothelial wall at sites of inflammation in order to fight infections.[39] Leukocytes from LAD-I patients are unable to adhere to endothelial cells and patients exhibit serious episodes of infection that can be life-threatening.
An
Pathogenic microorganisms, including bacteria, viruses and protozoans, have to first adhere to host cells in order to infect and cause diseases. Anti-adhesion therapy can be used to prevent infection by targeting adhesion molecules either on the pathogen or on the host cell.[41] Apart from altering the production of adhesion molecules, competitive inhibitors that bind to adhesion molecules to prevent binding between cells can also be used, acting as anti-adhesive agents.[42]
See also
- Cell communication (biology)
- Epithelium
- Cytoskeleton
- Differential adhesion hypothesis
- Role of cell adhesions in neural development
References
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External links
- The Cell by G. Cooper (online textbook)
- Molecular Cell Biology by Lodish et al. (online textbook)
- Molecular Biology of the Cell by Alberts et al. (online textbook)
- Cell Adhesion and Extracellular Matrix - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology