The laminin is a protein which is the extracellular matrix of basement membrane of epithelial tissues in vertebrates. This type of protein provides a binding support between the cells of the connective tissues, so that they function in the cohesion and compaction of these.
Generally, laminins are responsible for ordering the intricate protein network that makes up the extracellular matrix or basement membrane of tissues. Laminins are typically found associated with proteins such as collagen, proteoglycans, entactins, and heparan sulfates.
Laminins and their participation in the basement membrane of vertebrates (Source: Maiaaspe / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons)
This intricate basement membrane, ordered by laminins, separates the epithelial parts of the tissues, that is, each extracellular matrix separates the endothelium from the mesothelium and the extracellular matrix of the mesothelium separates this layer from the epithelium.
Much research has shown that the expression of mutated laminin genes is potentially lethal for a cell, as they are also responsible for regulating almost all complex interactions that occur within the basement membrane.
There is a great diversity of laminin families in all vertebrates. These vary in composition, form, function, and origin. In the same individual, in different tissues, different laminins can be found, each one adapted to the environment of the tissue that expresses it.
Characteristics of laminins
Laminin monomers or units are made up of a heterotrimer of three different glycoprotein chains. These proteins contain many different domains (multi-domains) and are essential parts for early embryonic tissue development.
The common shape of laminins is a kind of "cross" or "Y", although some are shaped like a long bar with four branches. This small variation allows each type of laminin to regulate proper integration from any position in the tissue.
Laminins have a high molecular weight, which can vary depending on the type of laminin, from 140 to 1000 kDa.
In general, each basement membrane has one or more different types of laminins within it, and some scientists propose that laminins determine a large part of the physiological function of the basement membranes of the tissue where they are found.
In vertebrate animals, at least 15 different types of laminins have been found, classified in a family, since they are formed from the same trimers, but with different combinations. In invertebrate animals between 1 and 2 different trimers have been found.
Current studies suggest that the laminins of all vertebrate animals arose through the differentiation of orthologous genes, that is, all the genes that code for laminins have a common origin from invertebrate animals.
Structure
Despite the large number of functions that laminins regulate, they have a fairly simple structure that, for the most part, is conserved among the different types that are known.
Each laminin is made up of three different chains intertwined with each other forming a kind of "interwoven fiber". Each of the three chains is identified as alpha (α), beta (β), and gamma (γ).
The formation of the trimer of each laminin depends on the union of the C-terminal region of each of its chains. Inside each molecule, these chains are paired through peptide bonds and three disulfide bridges that give the structure great mechanical strength.
Schematic diagram of the structure of a laminin (Source: Maiaaspe / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons)
Observations made by electron microscopy of typical laminin monomers have detailed that the structure is a kind of asymmetric cross that has a long arm of approximately 77 nm (nanometers) characterized by a prominent globular shape at one of its ends.
In addition, three short arms are observed, two at approximately 34 nm and one at approximately 48 nm. Each arm ends in a globular end, similar to that of the main chain, but smaller in size.
The difference between the different types of laminins is mainly due to the differences in the α chains, which can fold in at least three different ways; although currently variations have been identified for all chains:
- 5 different variations or chains of laminin α
- 3 variations of β chains
- 3 variations for γ chains
Features
The most important and commonly studied function of laminins is that of interaction with the receptors that anchor themselves on the cell membranes of cells adjacent to the basement membranes where they are found.
This interaction causes these proteins to be involved in the regulation of multiple cellular activities and signaling pathways. It should be mentioned that their functions depend on their interaction with specific receptors on the cell surface (many of the membrane receptors are currently classified according to their ability to bind to laminins).
Integrins are receptors that interact with laminins and "non-integrins" receptors are those that do not have the ability to bind to these proteins. Most of the “non-integrin” type receptors are proteoglycans, some dystroglycans or syndecans.
The maturation of the tissues of the body organs occurs with a replacement of early laminins, which were initially housed in the basement membrane of the tissues that made up the juvenile organs.
Among the laminins, the type that has been studied the most is laminin-1, which is directly linked to the growth of axons of practically any type of neuron under in vitro conditions, since these regulate the movement of the "growth cone" in the surface of neurons.
Nomenclature and types
Biochemists consider the laminin family to be a very large protein family, of which few of its members are still known. However, modern tools will allow new types of laminins to be glimpsed in a short time.
Such proteins are each identified with a number, starting with 1 ending the numbering at 15 (laminin-1, laminin-2… laminin-15).
Another type of nomenclature is also used, which indicates the type of chain that each laminin has. For example, laminin-11 is composed of an alpha (α) -5 chain, a beta (β) -2 chain, and a gamma (γ) -1 chain, so it can be named laminin-521.
In addition, each laminin is classified according to the function it is associated with and also according to the specific tissue of the body in which it participates. Some examples of laminins are:
- Lamina-1: involved in epithelial development
- Laminin-2: involved in the myogenic development of all tissues, the peripheral nervous system and the matrix of the glomeruli.
- Lamina-3: participates in myo-tendon junctions
- Lamina-4: works in the neuromuscular junctions and in the mesangial matrix of the glomeruli
- Laminin-5, 6 and 7: they act preferentially on epidermal tissues.
References
- Miner, JH, & Yurchenco, PD (2004). Laminin functions in tissue morphogenesis. Annu. Rev. Cell Dev. Biol., 20, 255-284.
- Rasmussen, DGK, & Karsdal, MA (2016). Laminins. In Biochemistry of Collagens, Laminins and Elastin (pp. 163-196). Academic Press.
- Sasaki, T., Fässler, R., & Hohenester, E. (2004). Laminin: the crux of basement membrane assembly. The Journal of cell biology, 164 (7), 959-963.
- Timpl, R., Engel, J., & Martin, GR (1983). Laminin-a multifunctional protein of basement membranes. Trends in Biochemical Sciences, 8 (6), 207-209.
- Timpl, R., Rohde, H., Robey, PG, Rennard, SI, Foidart, JM, & Martin, GR (1979). Laminin – a glycoprotein from basement membranes. Journal of Biological Chemistry, 254 (19), 9933-9937.
- Tryggvason, K. (1993). The laminin family. Current opinion in cell biology, 5 (5), 877-882.