Laminin: Definition, Function, Structure and Properties of These Glycoproteins

These high molecular mass proteins play several important roles.

Laminin is a protein that is a major component, with basement membrane collagen separating connective tissue, stromal cells, from epithelial tissues (lining of the mucosa or organs).

In the case of pathology, muscular dystrophies, neurological disorders (poor myelination of the nerves), skin or mucous membrane disorders can be observed .

Laminins are a major component of the basal lamina ECM protein.

In general, laminins are heterotrimeric glycoproteins with binding regions for collagen, integrins, cellular domains, and proteoglycans such as dystroglycan.

It also joins itself to form leaves in the basal lamina.

Laminins are composed of a central alpha chain of approximately 400 kDa with a variable number of globular regions and two chains of approximately 200 kDa (beta and gamma) with a-helical and globular helical regions.

Cysteine-rich repeats are prevalent in all laminin chains.

Laminin function

Basement membranes are sheet-like extracellular matrix structures that are the basis for cells to grow.

The composition of the basement membrane is highly selective for the cell surface and laminins are the key proteins that surround virtually all cells.

Laminins are important for embryogenesis and in the adult body, expression is tissue specific.

There are many binding sites on the full-length laminin molecule that can interact with receptors on the cell membrane.

Integrins are important laminin receptors, and the laminin-integrin interaction triggers vital intracellular signaling pathways.

By binding to specific cell receptors, laminins regulate cellular responses, such as cell anchoring, survival, proliferation, migration, organization, and specialization, leading to improved cell functionality.

Without the correct combination of laminin isoforms, cells and tissues become dysfunctional.

There are 15 different laminins, each of which consists of a unique combination of three substrings.

The combination of chains confers some tissue specificity.

Laminins are essential for basement membrane function as most null mutations are lethal.

Like collagens, laminins are structural proteins with a helical region made up of heptads.

Heptad has a less strict organization compared to collagens, where the helical domain consists of a strict building block of three amino acids.

Laminins play a central role in organizing complex basement membrane interactions.

This is seen through the wide range of interaction partners such as syndecan, nidogen, collagen, integrins, dystroglycan, and heparin.

Mutations in different laminin chains are associated with diseases such as Alport syndrome, epidermolysis bullosa, and muscular dystrophies.

The laminin family is large and biomarkers are emerging to measure laminins.

The essential role of laminins in the basement membrane can be summarized as follows: even the most exceptional construction will not last on a poor foundation.

Only full-length and intact lamina molecules can replicate the relevant biological conditions

Laminin structure

Laminins are multidomain, heterotrimeric, glycoproteins, composed of three different subunits; an α chain, β chain and γ chain.

The assembled laminin molecule forms a cross-type structure.

To date, there are at least 16 distinct isoforms identified in mammals and their names are derived from their combination of subunits, therefore the laminin 521 isoform has an alpha-5 / beta-2 / gamma-1 chain composition.

The molecular mechanism underlying laminin-mediated signaling has been suggested to involve the C-terminal region of laminins, but integrins and other cellular receptors also interact with some of the N-terminal globular domains.

Biolaminin Biolaminin substrates are the only original full-length recombinant laminins on the market.

A fractionated or truncated laminin molecule, or laminins isolated from tissue, lack many of the laminin domains that cells need to form the proper extracellular network and for the stimulation of correct cellular signal transductions.

Therefore, only a full-length, intact laminin can create a more authentic cell culture environment.

Laminins are a major component of the basement membrane, which is an intricate network of proteins that separates the epithelium, mesothelium, and endothelium from connective tissue.

Laminin properties

Laminin is a protein that shares several properties with fibronectin.

For example, it also has a high molecular weight. Laminin protein consists of three subunits, including α, β, and γ chains.

Laminins are also considered glycoproteins since they are functionalized with oligosaccharides.

In the extracellular matrix, laminin can bind to other laminin molecules, as well as other proteins such as collagen, helping to strengthen the structure of the extracellular matrix.

Cells can also bind to laminin through the integrin receptors that they express on their cell membranes.

These properties make laminins attractive for use as cell culture substrates for both pluripotent stem cells and neuronal cells.

Protocols to differentiate stem cells into mature phenotypes will often require culture on laminin 2D substrates.

Laminin also plays a key role in the development of the nervous system as axons tend to migrate onto this protein, making it attractive for regenerative medicine applications.

Finally, laminin is found in the neural stem cell niche, where it contributes its growth factor-binding properties to specialized structures known as fractons.

Laminins, the first detectable extracellular matrix glycoproteins in the embryo, are found in the basement membrane.

Laminin protein is detected in the infarct area on the third day after myocardial infarction, the concentration peaks on days 7-11, and then returns to baseline levels.

The extensive existence of laminins throughout the infarct area suggests that they may directly regulate left ventricular repair after myocardial infarction.

In patients with acute myocardial infarction, the serum laminin level is higher than in patients with stable coronary artery disease and those without coronary artery disease.

There is a possibility that serum laminin could be a potential prognostic marker for patients with myocardial infarction.