Laminins are high-molecular weight (~400 to ~900 kDa) proteins of the extracellular matrix. They are a major component of the basal lamina (one of the layers of the basement membrane), a protein network foundation for most cells and organs. The laminins are an important and biologically active part of the basal lamina, influencing cell differentiation, migration, and adhesion.
Laminins are heterotrimeric proteins that contain an α-chain, a β-chain, and a γ-chain, found in five, four, and three genetic variants, respectively.
The laminin molecules are named according to their chain composition. Thus, laminin-511 contains α5, β1, and γ1 chains. Fourteen other chain combinations have been identified in vivo.
The trimeric proteins intersect to form a cross-like structure that can bind to other cell membrane and extracellular matrix molecules. The three shorter arms are particularly good at binding to other laminin molecules, which allows them to form sheets. The long arm is capable of binding to cells, which helps anchor organized tissue cells to the membrane.
The laminin family of glycoproteins are an integral part of the structural scaffolding in almost every tissue of an organism. They are secreted and incorporated into cell-associated extracellular matrices.
Laminin is vital for the maintenance and survival of tissues. Defective laminins can cause muscles to form improperly, leading to a form of muscular dystrophy, lethal skin blistering disease (junctional epidermolysis bullosa) and defects of the kidney filter (nephrotic syndrome).
Types Of Laminins
Fifteen laminin trimers have been identified. The laminins are combinations of different alpha-, beta-, and gamma-chains.
The five forms of alpha-chains are: LAMA1, LAMA2, LAMA3 (which has three splice forms), LAMA4, LAMA5
The beta-chains include: LAMB1, LAMB2, LAMB3, LAMB4 (note that no known laminin trimer incorporates LAMB4 and its function remains poorly understood)
The gamma-chains are: LAMC1, LAMC2, LAMC3
Laminins were previously numbered as they were discovered, i.e. laminin-1, laminin-2, laminin-3, etc., but the nomenclature was changed to describe which chains are present in each isoform (laminin-111, laminin-211, etc.). In addition, many laminins had common names before either laminin nomenclature was in place.
Laminins form independent networks and are associated with type IV collagen networks via entactin, fibronectin, and perlecan. They also bind to cell membranes through integrin receptors and other plasma membrane molecules, such as the dystroglycan glycoprotein complex and Lutheran blood group glycoprotein.
Through these interactions, laminins critically contribute to cell attachment and differentiation, cell shape and movement, maintenance of tissue phenotype, and promotion of tissue survival.
Some of these biological functions of laminin have been associated with specific amino-acid sequences or fragments of laminin. For example, the peptide sequence [GTFALRGDNGDNGQ], which is located on the alpha-chain of laminin, promotes adhesion of endothelial cells.
Laminin alpha4 is distributed in a variety of tissues including peripheral nerves, dorsal root ganglion, skeletal muscle and capillaries; in the neuromuscular junction, it is required for synaptic specialisation. The structure of the laminin-G domain has been predicted to resemble that of pentraxin.
Dysfunctional structure of one particular laminin, laminin-211, is the cause of one form of congenital muscular dystrophy. Laminin-211 is composed of an α2, a β1 and a γ1 chains. This laminin’s distribution includes the brain and muscle fibers. In muscle, it binds to alpha dystroglycan and integrin alpha7—beta1 via the G domain, and via the other end binds to the extracellular matrix.
Abnormal laminin-332, which is essential for epithelial cell adhesion to the basement membrane, leads to a condition called junctional epidermolysis bullosa, characterized by generalized blisters, exuberant granulation tissue of skin and mucosa, and pitted teeth.
Malfunctional laminin-521 in the kidney filter causes leakage of protein into the urine and nephrotic syndrome.
Timpl R, Rohde H, Robey PG, Rennard SI, Foidart JM, Martin GR (October 1979)
Laminin – a glycoprotein from basement membranes
The Journal of Biological Chemistry. 254 (19): 9933–7
Top Image: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute. Crystal structure of three consecutive laminin-type epidermal growth factor-like (le) modules of laminin gamma1 chain harboring the nidogen binding site.