Laminin
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Laminins are a
glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to biological activity, influencing cell differentiation, migration, and adhesion.[1][2]
Laminins are
paralogous genes in humans, respectively. The laminin molecules are named according to their chain composition, e.g. laminin-511 contains α5, β1, and γ1 chains.[3] Fourteen other chain combinations have been identified in vivo. The trimeric proteins intersect, composing a cruciform structure that is able to bind to other molecules of the extracellular matrix and cell membrane.[4]
The three short arms have an affinity for binding to other laminin molecules, conducing sheet formation. The long arm is capable of binding to cells and helps anchor organized tissue cells to the basement membrane.
Laminins are integral to the structural scaffolding of almost every tissue of an organism—secreted and incorporated into cell-associated extracellular matrices. These glycoproteins are imperative to the maintenance and vitality 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/or defects of the kidney filter (nephrotic syndrome).[5]
Types
In humans, fifteen laminin trimers have been identified. The laminins are combinations of different alpha-, beta-, and gamma-chains.[6]
- Five alpha-chain isoforms: LAMA5
- Four beta-chain isoforms: LAMB4(note that no known laminin trimer incorporates LAMB4 and its function remains poorly understood)
- Three gamma-chain isoforms: 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.).[3] In addition, many laminins had common names before either laminin nomenclature was in place.[7][8]
| Old nomenclature | Old synonyms | Chain composition | New nomenclature |
|---|---|---|---|
| Laminin-1 | EHS laminin | α1β1γ1 | Laminin-111 |
| Laminin-2 | Merosin | α2β1γ1 | Laminin-211 |
| Laminin-3 | S-laminin | α1β2γ1 | Laminin-121 |
| Laminin-4 | S-merosin | α2β2γ1 | Laminin-221 |
| Laminin-5 / Laminin-5A | Kalinin, epiligrin, nicein, ladsin | α3Aβ3γ2 | Laminin-332 / Laminin-3A32 |
| Laminin-5B | α3Bβ3γ2 | Laminin-3B32 | |
| Laminin-6 / Laminin-6A | K-laminin | α3Aβ1γ1 | Laminin-311 / Laminin-3A11 |
| Laminin-7 / Laminin-7A | KS-laminin | α3Aβ2γ1 | Laminin-321 / Laminin-3A21 |
| Laminin-8 | α4β1γ1 | Laminin-411 | |
| Laminin-9 | α4β2γ1 | Laminin-421 | |
| Laminin-10 | Drosophila-like laminin | α5β1γ1 | Laminin-511 |
| Laminin-11 | α5β2γ1 | Laminin-521 | |
| Laminin-12 | α2β1γ3 | Laminin-213 | |
| Laminin-14 | α4β2γ3 | Laminin-423 | |
| α5β2γ2 | Laminin-522 | ||
| Laminin-15 | α5β2γ3 | Laminin-523 |
Function
Laminins form independent networks and are associated with
plasma membrane molecules, such as the dystroglycan glycoprotein complex and Lutheran blood group glycoprotein.[4] Through these interactions, laminins critically contribute to cell attachment and differentiation, cell shape and movement, maintenance of tissue phenotype, and promotion of tissue survival.[4][6] Some of these biological functions of laminin have been associated with specific amino-acid sequences or fragments of laminin.[4] For example, the peptide sequence [GTFALRGDNGDNGQ], which is located on the alpha-chain of laminin, promotes the adhesion of endothelial cells.[11]
Laminin alpha4 is distributed in a variety of
pentraxin.[13]
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
tectum. It is also often used as a substrate in cell culture experiments. 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.[citation needed] This effect of laminin-111 probably occurs through a lowering of intracellular cyclic AMP.[citation needed
]
Role in peripheral nerve repair
Laminins are enriched at the lesion site after peripheral nerve injury and are secreted by Schwann cells. Neurons of the peripheral nervous system express integrin receptors that attach to laminins and promote neuroregeneration after injury.[14]
Pathology
Dysfunctional structure of one particular laminin, laminin-211, is the cause of one form of
beta1 via the G domain, and via the other end, it binds to the extracellular matrix
.
Abnormal laminin-332, essential for epithelial cell adhesion to the basement membrane, leads to 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.[5]
Role in cancer
 | This section's tone or style may not reflect the encyclopedic tone used on Wikipedia. (July 2012) |
Some of the laminin isoforms have been implicated in
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. The IRES activity of LamB1 was determined by independent bicistronic reporter assays. Strong evidence excludes 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. RNA affinity purification demonstrated that the La protein interacts with the LamB1 IRES. This interaction and its regulation during EMT were confirmed by ribonucleoprotein immunoprecipitation. La is able to positively modulate LamB1 IRES translation, so LamB1 IRES is activated by binding to La which leads to translational upregulation during hepatocellular EMT.[16]
Use in cell culture
Together with other major components of the ECM, such as
recombinant laminins have been produced since the year 2000.[18] This made it possible to 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 cells can be grown for months on top of recombinant laminin-511.[19][20] Later, Rodin et al. showed that recombinant laminin-511 can be used to create a xeno-free and defined cell culture environment to culture human pluripotent ES cells and human iPS cells.[21]
Laminin domains
| Laminin Domain I | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Laminin_I | ||||||||
| Pfam | PF06008 | ||||||||
| InterPro | IPR009254 | ||||||||
| |||||||||
| Laminin Domain II | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Laminin_II | ||||||||
| Pfam | PF06009 | ||||||||
| InterPro | IPR010307 | ||||||||
| |||||||||
| Laminin B (Domain IV) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Laminin_B | ||||||||
| Pfam | PF00052 | ||||||||
| InterPro | IPR000034 | ||||||||
| |||||||||
| Laminin EGF-like (Domains III and V) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| |||||||||
| Laminin G domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| |||||||||
| Laminin G domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 the structure of the ligand-binding domain of neurexin 1beta: regulation of lns domain function by alternative splicing | |||||||||
| Identifiers | |||||||||
| Symbol | Laminin_G_2 | ||||||||
| Pfam | PF02210 | ||||||||
| Pfam clan | CL0004 | ||||||||
| InterPro | IPR012680 | ||||||||
| SMART | TSPN | ||||||||
| |||||||||
| Laminin N-terminal (Domain VI) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Laminin_N | ||||||||
SCOP2 | 1klo / SCOPe / SUPFAM | ||||||||
| |||||||||
Laminins contain several
protein domains
.
Laminin I and Laminin II
Laminins are trimeric molecules; laminin-1 is an alpha1 beta1 gamma1
structure.[22]
Laminin B
The laminin B domain (also known as domain IV) is an
heparan sulphate proteoglycan from basement membrane, a laminin-like protein from Caenorhabditis elegans
and laminin. Laminin IV domain is not found in short laminin chains (alpha4 or beta3).
Laminin EGF-like
Beside different types of globular
loops C1-C3 and C5-C6.[24][25] Long consecutive arrays of laminin EGF-like domains in laminins form rod-like elements of limited flexibility, which determine the spacing in the formation of laminin networks of basement membranes.[27][28]
Laminin G
The laminin globular (G) domain, also known as the LNS (Laminin-alpha, Neurexin and Sex hormone-binding globulin) domain, is on average 177
extracellular proteins.[29] For example, all laminin alpha-chains have five laminin G domains, all collagen
family proteins have one laminin G domain, the CNTNAP proteins have four laminin G domains, while neurexin 1 and 2 each hold six laminin G domains. On average, approximately one quarter of the proteins that hold laminin G domains is taken up by these laminin G domains themselves. The smallest laminin G domain can be found in one of the collagen proteins (COL24A1; 77 AA) and the largest domain in TSPEAR (219 AA).
The exact function of the Laminin G
differentiation
.
Laminin N-terminal
integrins and dystroglycan (and possibly other receptors) recruited to the adherent laminin. This LN domain-dependent self-assembly is considered to be crucial for the integrity of basement membranes, as highlighted by genetic forms of muscular dystrophy containing the deletion of the LN module from the alpha 2 laminin chain.[31] The laminin N-terminal domain is found in all laminin and netrin subunits
except laminin alpha 3A, alpha 4 and gamma 2.
Human proteins containing laminin domains
- Laminin domain I: all laminin alpha chains (LAMA5)
- Laminin domain II: all laminin alpha chains (LAMA5)
- Laminin B (domain IV): all laminin alpha chains (HSPG2)
- Laminin EGF-like (domains III and V): all laminin chains ().
- Laminin G domain: all laminin alpha chains (SHBG) and usherin (USH2A)
- Laminin N-terminal (domain VI): most laminin chains (NTNG2), and usherin (USH2A)
See also
References
- PMID 114518.
- PMID 19693542– via Springer Link.
- ^ PMID 15979864.
- ^ ISBN 978-0-19-963220-6.
- ^ PMID 19355968.
- ^ PMID 10842354.
- ISBN 9780471251859.
- ISBN 9780412138614.
- PMID 8208674.
- PMID 7904354.
- ^ Beck et al., 1999.[specify]
- PMID 15823034.
- PMID 9480764.
- PMID 29446228.
- PMID 17438294.
- PMID 21896617.
- PMID 16289578.
- PMID 10809728.
- PMID 18757303.
- PMID 18675790.
- S2CID 10801152.
- PMID 3182802.
- S2CID 36607427.
- ^ PMID 8648630.
- ^ PMID 8648631.
- S2CID 21559588.
- PMID 2404817.
- ^ PMID 8349613.
- ^ "Laminin G domain". InterPro. European Bioinformatics Institute. Retrieved 22 February 2016.
- PMID 10747011.
- S2CID 21549628.
External links
Wikiquote has quotations related to Laminin.
- The Laminin Protein
- Laminin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P19137 (Laminin subunit alpha-1) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: P24043 (Laminin subunit alpha-2) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: O15230 (Laminin subunit alpha-5) at the PDBe-KB.
- "How I learned to love laminin". YouTube. Imperial College London. April 13, 2011. (lecture by Professor Erhard Hoheneseter)