Laminin
Encyclopedia
Laminins are major proteins in 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, adhesion as well as phenotype and survival.
Laminins are trimeric 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 laminins are a family of glycoprotein
s that 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
).
Laminins were previously called Laminin-1, Laminin-2 etc… but the nomenclature was recently changed to describe which chains are present in each isoform. For example, laminin-511 contains an α5-chain, a β1-chain and a γ1 chain.
networks via entactin
, fibronectin
, and perlecan
. They also bind to cell membranes through integrin
receptor
s 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-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 cells, leads to dissociation of keratinocytes of the skin and cells covering the gastrointestinal tract from the basal lamina with severe skin blisters and loss of cells in the mouth, pharynx, and gastrointestinal tract. A called congential muscular dystrophy that leads to death in early infancy. Malfunctional laminin-521 in the kidney filter causes leakage of protein into the urine and nephrotic syndrome.
;
; ATRN
; ATRNL1; CELSR1
; CELSR2
; CELSR3
; CRELD1
; HSPG2;
LAMA1; LAMA2; LAMA3; LAMA4; LAMA5; LAMB1; LAMB2; LAMB3;
LAMB4
; LAMC1; LAMC2; LAMC3
; MEGF10
; MEGF12; MEGF6;
MEGF8; MEGF9; NSR1; NTN1
; NTN2L; NTN4; NTNG1
; NTNG2
;
RESDA1; SCARF1; SCARF2; SREC; STAB1
; USH2A
;
; CASPR4; CELSR1
; CELSR2
; CELSR3
; CNTNAP1; CNTNAP2
; CNTNAP3; CNTNAP4
;
CNTNAP5; COL11A1
; COL11A2
; COL24A1
; COL5A1
; COL5A3
; CRB1
; CRB2;
CSPG4
; EGFLAM; FAT
; FAT2; FAT4
; GAS6
; HSPG2; LAMA1;
LAMA2; LAMA3; LAMA4; LAMA5; NELL2
; NRXN1
; NRXN2
; NRXN3
;
PROS1; RESDA1; SLIT1
; SLIT2
; SLIT3
; USH2A
;
;
LAMC1; LAMC3
; NTN1
; NTN2L; NTN4; NTNG1
; NTNG2
; USH2A
;
Basal lamina
The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often confused with the basement membrane, and sometimes used inconsistently in the literature, see below....
(one of the layers of the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
), 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, adhesion as well as phenotype and survival.
Laminins are trimeric 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 laminins are a family of glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s that 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
Junctional epidermolysis bullosa (medicine)
Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.Types include:Another form, cicatricial junctional epidermolysis bullosa, is not included in OMIM....
) and defects of the kidney filter (nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
).
Types
Fifteen laminin trimers have been identified. The laminins are combinations of different alpha-, beta-, and gamma-chains.- There are five forms of alpha-chains: LAMA1, LAMA2, LAMA3, LAMA4, LAMA5
- There are four of beta-chains: LAMB1, LAMB2, LAMB3, LAMB4LAMB4LAMB4 is a laminin gene....
- There are three of gamma-chains: LAMC1, LAMC2, LAMC3LAMC3Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.- Function :Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes...
Laminins were previously called Laminin-1, Laminin-2 etc… but the nomenclature was recently changed to describe which chains are present in each isoform. For example, laminin-511 contains an α5-chain, a β1-chain and a γ1 chain.
Networks
Laminins form independent networks and are associated with type IV collagenCollagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
networks via entactin
Entactin
Entactin also known as nidogen-1 is a protein that in humans is encoded by the NID1 gene. Entactin is a component of the basement membrane alongside other components such as collagen type IV, proteoglycans , laminin and fibronectin.- Function :Entactin is a member of the nidogen family of basement...
, fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
, and perlecan
Perlecan
Perlecan also known as basement membrane-specific heparan sulfate proteoglycan core protein or heparan sulfate proteoglycan 2 , is a protein that in humans is encoded by the HSPG2 gene....
. They also bind to cell membranes through integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s and other plasma membrane molecules, such as the dystroglycan
Dystroglycan
Dystroglycan is a protein that in humans is encoded by the DAG1 gene.Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens by chromosome 3. There are two exons that are separated by a large intron...
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
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
sequence [GTFALRGDNGDNGQ], which is located on the alpha-chain of laminin, promotes adhesion of endothelial cells.
Pathology
Dysfunctional structure of one particular laminin, laminin-211, is the cause of one form of congenital muscular dystrophyCongenital muscular dystrophy
Congenital muscular dystrophy is the term used to describe muscular dystrophy that is present at birth. CMD describes a number of autosomal recessive diseases of muscle weakness and possible joint deformities, present at birth and slowly progressing...
. Laminin-211 is composed of an α2
Laminin, alpha 2
Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.- Function :Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by...
, a β1
Laminin, beta 1
Laminin subunit beta-1 is a protein that in humans is encoded by the LAMB1 gene.-Further reading:...
and a γ1
Laminin, gamma 1
Laminin subunit gamma-1 is a protein that in humans is encoded by the LAMC1 gene.-Further reading:...
chains. This laminin's distribution includes the brain and muscle fibers. In muscle, it binds to alpha dystroglycan
Dystroglycan
Dystroglycan is a protein that in humans is encoded by the DAG1 gene.Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens by chromosome 3. There are two exons that are separated by a large intron...
and integrin alpha7
ITGA7
Integrin alpha-7 is a protein that in humans is encoded by the ITGA7 gene.-Interactions:ITGA7 has been shown to interact with FHL2 and FHL3.-External links:* Info with links in the...
—beta1
CD29
Integrin beta-1 is a protein that in humans is encoded by the ITGB1 gene. CD29 is an integrin unit associated with very late antigen receptors. It is known to conjoin with alpha-3 subunit to create α3β1 complex that reacts to such molecules as netrin-1 and reelin.Integrins are heterodimeric...
via the G domain, and via the other end binds to the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
. Abnormal laminin-332, which is essential for epithelial cells, leads to dissociation of keratinocytes of the skin and cells covering the gastrointestinal tract from the basal lamina with severe skin blisters and loss of cells in the mouth, pharynx, and gastrointestinal tract. A called congential muscular dystrophy that leads to death in early infancy. Malfunctional laminin-521 in the kidney filter causes leakage of protein into the urine and nephrotic syndrome.
Laminins in cell culture
Recently, several publications have demonstrated that laminins can be used to culture cells, such as pluripotent stem cells, that are difficult to culture on other substrates. Mostly two types of laminins have been used. Laminin-111 extracted from mouse sarcomas is one popular laminin type, as well as a mixture of laminins 511 and 521 from human placenta. Various laminin isoforms are practically impossible to isolate from tissues in pure form due to extensive cross-linking and the need for harsh extraction conditions such as proteolytic enzymes or low pH that cause degradation. However, professor Tryggvason's group at the Karolinska Institute in Sweden showed how to produce recombinant laminins using HEK293 cells in 2000. Kortesmaa et al. 2000. This opened the possibility test if laminins could have a significant role in vitro as they have in the human body. In 2008, two groups independently showed that mouse embryonic stem cell can be grown for months on top of recombinant laminin-511.Later on Rodin et al showed that recombinant laminin 511 can be used to create a totally xenon-free and defined cell culture environment to culture human pluripotent ES cells and human iPS cells.Role in neural development
Laminin-111 is a major substrate along which nerve axons will grow, both in vivo and in vitro. For example, it lays down a path that developing retinal ganglion cells follow on their way from the retina to the tectum. It is also often used as a substrate in cell culture experiments. Interestingly, the presence of laminin-1 can influence how the growth cone responds to other cues. For example, growth cones are repelled by netrin when grown on laminin-111, but are attracted to netrin when grown on fibronectin. This effect of laminin-111 probably occurs through a lowering of intracellular cyclic AMP.Role in cancer
The majority of transcripts that harbor an internal ribosome entry site (IRES) are involved in cancer development via corresponding proteins. A crucial event in tumor progression referred to as epithelial to mesenchymal transition (EMT) allows carcinoma cells to acquire invasive properties. The translational activation of the extracellular matrix component laminin B1 (LamB1) during EMT has been recently reported suggesting an IRES-mediated mechanism. In this study, the IRES activity of LamB1 was determined by independent bicistronic reporter assays. Strong evidences exclude an impact of cryptic promoter or splice sites on IRES-driven translation of LamB1. Furthermore, no other LamB1 mRNA species arising from alternative transcription start sites or polyadenylation signals were detected that account for its translational control. Mapping of the LamB1 5'-untranslated region (UTR) revealed the minimal LamB1 IRES motif between -293 and -1 upstream of the start codon. Notably, RNA affinity purification showed that the La protein interacts with the LamB1 IRES. This interaction and its regulation during EMT were confirmed by ribonucleoprotein immunoprecipitation. In addition, La was able to positively modulate LamB1 IRES translation. In summary, these data indicate that the LamB1 IRES is activated by binding to La which leads to translational upregulation during hepatocellular EMT.Laminin B (Domain IV)
HSPG2; LAMA1; LAMA2; LAMA3; LAMA5; LAMC1; LAMC2; LAMC3LAMC3
Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.- Function :Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes...
;
Laminin EGF-like (Domains III and V)
AGRINAgrin
Agrin is a large proteoglycan whose best characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN...
; ATRN
ATRN
Attractin is a protein that in humans is encoded by the ATRN gene.Attractin is a Group XI C-type lectin.-Further reading:...
; ATRNL1; CELSR1
CELSR1
Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the CELSR1 gene.- Function :...
; CELSR2
CELSR2
Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the CELSR2 gene.-Further reading:...
; CELSR3
CELSR3
Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the CELSR3 gene.- Further reading :...
; CRELD1
CRELD1
Cysteine-rich with EGF-like domain protein 1 is a protein that in humans is encoded by the CRELD1 gene.-Further reading:...
; HSPG2;
LAMA1; LAMA2; LAMA3; LAMA4; LAMA5; LAMB1; LAMB2; LAMB3;
LAMB4
LAMB4
LAMB4 is a laminin gene....
; LAMC1; LAMC2; LAMC3
LAMC3
Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.- Function :Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes...
; MEGF10
MEGF10
Multiple EGF-like-domains 10 is a protein that in humans is encoded by the MEGF10 gene.MEGF10 is a a regulator of satellite cell myogenesis. It has been shown to be the cause of onset myopathy, areflexia, respiratory distress and dysphagia....
; MEGF12; MEGF6;
MEGF8; MEGF9; NSR1; NTN1
NTN1
Netrin-1 is a protein that in humans is encoded by the NTN1 gene.Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development...
; NTN2L; NTN4; NTNG1
NTNG1
Netrin-G1 is a protein that in humans is encoded by the NTNG1 gene.-Further reading:...
; NTNG2
NTNG2
Netrin-G2 is a protein that in humans is encoded by the NTNG2 gene.-Further reading:...
;
RESDA1; SCARF1; SCARF2; SREC; STAB1
STAB1
Stabilin-1 is a protein that in humans is encoded by the STAB1 gene.-Further reading:...
; USH2A
USH2A
Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:...
;
Laminin G domain
AGRINAgrin
Agrin is a large proteoglycan whose best characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN...
; CASPR4; CELSR1
CELSR1
Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the CELSR1 gene.- Function :...
; CELSR2
CELSR2
Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the CELSR2 gene.-Further reading:...
; CELSR3
CELSR3
Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the CELSR3 gene.- Further reading :...
; CNTNAP1; CNTNAP2
CNTNAP2
Contactin-associated protein-like 2 is a protein that in humans is encoded by the CNTNAP2 gene.This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal...
; CNTNAP3; CNTNAP4
CNTNAP4
Contactin-associated protein-like 4 is a protein that in humans is encoded by the CNTNAP4 gene.-Further reading:...
;
CNTNAP5; COL11A1
COL11A1
Collagen alpha-1 chain is a protein that in humans is encoded by the COL11A1 gene.- Function :The COL11A1 gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1...
; COL11A2
COL11A2
COL11A2 is a human gene that is one of several genes that provide instructions for the production of type XI collagen. The COL11A2 gene produces one component of this type of collagen, called the pro-alpha2 chain...
; COL24A1
COL24A1
COL24A1 is a collagen gene....
; COL5A1
COL5A1
Collagen alpha-1 chain is a protein that in humans is encoded by the COL5A1 gene.-External links:*...
; COL5A3
COL5A3
Collagen alpha-3 chain is a protein that in humans is encoded by the COL5A3 gene.-Further reading:...
; CRB1
CRB1
Crumbs homolog 1 is a protein that in humans is encoded by the CRB1 gene.This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors...
; CRB2;
CSPG4
CSPG4
Chondroitin sulfate proteoglycan 4 or melanoma-associated chondroitin sulfate proteoglycan is a chondroitin sulfate proteoglycan that in humans is encoded by the CSPG4 gene....
; EGFLAM; FAT
FAT (gene)
Protocadherin Fat 1 is a protein that in humans is encoded by the FAT1 gene.-Further reading:...
; FAT2; FAT4
FAT4
Protocadherin Fat 4, also known as cadherin family member 14 or FAT tumor suppressor homolog 4 , is a protein that in humans is encoded by the FAT4 gene.FAT4 is associated with the Hippo signaling pathway....
; GAS6
GAS6
Growth arrest-specific 6, also known as GAS6, is a human gene coding for the Gas6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity...
; HSPG2; LAMA1;
LAMA2; LAMA3; LAMA4; LAMA5; NELL2
NELL2
Protein kinase C-binding protein NELL2 is an enzyme that in humans is encoded by the NELL2 gene.-Further reading:...
; NRXN1
NRXN1
Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene.-Genomics:The gene is found in a single copy on the short arm of chromosome 2 . The gene is 1,112,187 bases in length, is located on the Crick strand and encodes a protein of 1,477 amino acids .-Further reading:...
; NRXN2
NRXN2
Neurexin-2-alpha is a protein that in humans is encoded by the NRXN2 gene.-Further reading:...
; NRXN3
NRXN3
Neurexin-3-alpha is a protein that in humans is encoded by the NRXN3 gene.-Further reading:...
;
PROS1; RESDA1; SLIT1
SLIT1
Slit homolog 1 protein is a protein that in humans is encoded by the SLIT1 gene.-Further reading:...
; SLIT2
SLIT2
Slit homolog 2 protein is a protein that in humans is encoded by the SLIT2 gene.-Interactions:SLIT2 has been shown to interact with Glypican 1.-Further reading:...
; SLIT3
SLIT3
Slit homolog 3 protein is a protein that in humans is encoded by the SLIT3 gene.-Further reading:...
; USH2A
USH2A
Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:...
;
Laminin N-terminal (Domain VI)
LAMA1; LAMA2; LAMA3; LAMA5; LAMB1; LAMB2; LAMB3; LAMB4LAMB4
LAMB4 is a laminin gene....
;
LAMC1; LAMC3
LAMC3
Laminin subunit gamma-3 also known as LAMC3 is a protein that in humans is encoded by the LAMC3 gene.- Function :Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes...
; NTN1
NTN1
Netrin-1 is a protein that in humans is encoded by the NTN1 gene.Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development...
; NTN2L; NTN4; NTNG1
NTNG1
Netrin-G1 is a protein that in humans is encoded by the NTNG1 gene.-Further reading:...
; NTNG2
NTNG2
Netrin-G2 is a protein that in humans is encoded by the NTNG2 gene.-Further reading:...
; USH2A
USH2A
Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:...
;