| 1. |
- Sasaki, T, et al.
(author)
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Expression and distribution of laminin alpha 1 and alpha 2 chains in embryonic and adult mouse tissues: An immunochemical approach
- 2002
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In: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 275:2, s. 185-199
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Journal article (peer-reviewed)abstract
- Protein levels, mRNA expression, and localization of laminin alpha1 and alpha2 chains in development and in adult mice were examined. Recombinant fragments were used to obtain high-titer-specific polyclonal antibodies for establishing quantitative radioimmuno-inhibition assays. This often demonstrated an abundance of alpha2 chain, but also distinct amounts of alpha1 chain for adult tissues. The highest amounts of alpha1 were found in placenta, kidney, testis, and liver and exceeded those of alpha2. All other tissue extracts showed a higher content of alpha2, which was particularly high in heart and muscle when compared to alpha1. Content of gamma1 chain, shared by most laminins, was also analyzed. This demonstrated gamma1 chain levels being equal to or moderately exceeding the sum of alpha1 and alpha2 chains, indicating that these isoforms represent the major known laminin isoforms in most adult mouse tissues so far examined. Moreover, we found good correlation between radioimmuno-inhibition data and mRNA levels of adult tissues as measured by quantitative real-time reverse transcriptase-PCR. Embryonic tissues were also analyzed by radioimmuno-inhibition assays. This demonstrated for day 11 embryos comparable amounts of alpha1 and gamma1 and a more than 25-fold lower content of alpha2. This content increased to about 10% of alpha1 in day 13 embryos. The day 18 embryo showed in heart, kidney, and liver, but not yet in brain and lung, alpha1/alpha2 chain ratios comparable to those in adult tissues. Immunostaining demonstrated alpha1 in Reichert's membrane (day 7.5), while alpha2 could not be detected before day 11.5. These data were compared with immunohistochemical localization results on several more embryonic and adult tissue sections. Our results regarding localization are consistent with those of earlier work with some notable exceptions. This was in part due to epitope masking for monoclonal antibodies commonly used in previous studies in esophagus, intestine, stomach, liver, kidney, and spleen. (C) 2002 Elsevier Science (USA).
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| 2. |
- Aumailley, M, et al.
(author)
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A simplified laminin nomenclature
- 2005
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In: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 24:5, s. 326-332
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Research review (peer-reviewed)abstract
- A simplification of the laminin nomenclature is presented. Laminins are multidomain heterotrimers composed of alpha, beta and gamma chains. Previously, laminin trimers were numbered with Arabic numerals in the order discovered, that is laminins-1 to -5. We introduce a new identification system for a trimer using three Arabic numerals, based on the alpha, beta and gamma chain numbers. For example, the laminin with the chain composition alpha 5 beta 1 gamma 1 is termed laminin-511, and not laminin-10. The current practice is also to mix two overlapping domain and module nomenclatures. Instead of the older Roman numeral nomenclature and mixed nomenclature, all modules are now called domains. Some domains are renamed or renumbered. Laminin epidermal growth factor-like (LE) domains are renumbered starting at the N-termini, to be consistent with general protein nomenclature. Domain IVb of alpha chains is named laminin 4a (L4a), domain IVa of alpha chains is named L4b, domain IV of gamma chains is named L4, and domain IV of beta chains is named laminin four (LF). The two coiled-coil domains I and II are now considered one laminin coiled-coil domain (LCC). The interruption in the coiled-coil of 13 chains is named laminin beta-knob (L beta) domain. The chain origin of a domain is specified by the chain nomenclature, such as alpha IL4a. The abbreviation LM is suggested for laminin. Otherwise, the nomenclature remains unaltered.
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| 3. |
- Ekblom, Peter, et al.
(author)
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Expression and biological role of laminin-1.
- 2003
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In: Matrix Biology. - 1569-1802. ; 22:1, s. 35-47
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Research review (peer-reviewed)abstract
- Of the approximately 15 laminin trimers described in mammals, laminin-1 expression seems to be largely limited to epithelial basement membranes. It appears early during epithelial morphogenesis in most tissues of the embryo, and remains present as a major epithelial laminin in some adult tissues. Previous organ culture studies with embryonic tissues have suggested that laminin-1 is important for epithelial development. Recent data using genetically manipulated embryonic stem (ES) cells grown as embryoid bodies provide strong support for the view of a specific role of laminin-1 in epithelial morphogenesis. One common consequence of genetic ablation of FGF signaling, beta1-integrin or laminin gamma1 chain expression in ES cells is the absence of laminin-1, which correlates with failure of BM assembly and epiblast differentiation. Partial but distinct rescue of epiblast differentiation has been achieved in all three mutants by exogenously added laminin-1. Laminin-1 contains several biologically active modules, but several are found in beta1 or gamma1 chains shared by at least 11 laminins. However, the carboxytermini of the alpha chains contain five laminin globular (LG) modules, distinct for each alpha chain. There is increasing evidence for a particular role of alpha1LG4 binding to its receptors for epithelial tubulogenesis. The biological roles of this and other domains of laminin-1 are currently being explored by genetic means. The pathways controlling laminin-1 synthesis have remained largely unknown, but recent advances raise the possibility that laminin-1 and collagen IV synthesis can be regulated by pro-survival kinases of the protein kinase B/Akt family.
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| 4. |
- Ferletta, Maria, et al.
(author)
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Opposing roles of integrin alpha6Abeta1 and dystroglycan in laminin-mediated extracellular signal-regulated kinase activation
- 2003
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In: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 14:5, s. 2088-2103
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Journal article (peer-reviewed)abstract
- Laminin-integrin interactions can in some settings activate the extracellular signal-regulated kinases (ERKs) but the control mechanisms are poorly understood. Herein, we studied ERK activation in response to two laminins isoforms (-1 and -10/11) in two epithelial cell lines. Both cell lines expressed beta1-containing integrins and dystroglycan but lacked integrin alpha6beta4. Antibody perturbation assays showed that both cell lines bound to laminin-10/11 via the alpha3beta1and alpha6beta1 integrins. Although laminin-10/11 was a stronger adhesion complex than laminin-1 for both cell lines, both laminins activated ERK in only one of the two cell lines. The ERK activation was mediated by integrin alpha6beta1 and not by alpha3beta1 or dystroglycan. Instead, we found that dystroglycan-binding domains of both laminin-1 and -10/11 suppressed integrin alpha6beta1-mediated ERK activation. Moreover, the responding cell line expressed the two integrin alpha6 splice variants, alpha6A and alpha6B, whereas the nonresponding cell line expressed only alpha6B. Furthermore, ERK activation was seen in cells transfected with the integrin alpha6A subunit, but not in alpha6B-transfected cells. We conclude that laminin-1 and -10/11 share the ability to induce ERK activation, that this is regulated by integrin alpha6Abeta1, and suggest a novel role for dystroglycan-binding laminin domains as suppressors of this activation.
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| 5. |
- Kikkawa, Yamato, et al.
(author)
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Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of beta1 integrin-null cells.
- 2004
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In: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 300:1, s. 94-108
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Journal article (peer-reviewed)abstract
- The presence of many laminin receptors of the β1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin α6β4 and dystroglycan. We therefore tested the binding of a β1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin α6Aβ4A variant. GD25 β1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin α6 antibody, but not by a dystroglycan antibody. Hence, integrin α6Aβ4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin α6Aβ4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin α6Aβ4A.
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| 6. |
- Kvist, Alexander, et al.
(author)
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The major basement membrane components localize to the chondrocyte pericellular matrix - A cartilage basement membrane equivalent?
- 2008
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In: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 27:1, s. 22-33
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Journal article (peer-reviewed)abstract
- In this study, we demonstrate that articular cartilage chondrocytes are surrounded by the defining basement membrane proteins laminin, collagen type IV, nidogen and perlecan, and suggest that these form the functional equivalent of a basement membrane. We found by real-time PCR that mouse chondrocytes express these four cardinal components of basement membranes and demonstrated by immunohistochemistry that the proteins are present in bovine and mouse cartilage tissues and are deposited in a thin pericellular structure. Immunoelectron microscopy confirmed high laminin concentration in the pericellular matrix. In cartilage from newborn mice, basement membrane components are widespread in the territorial and interterritorial matrix, while in mature cartilage of adult mice the basement membrane components are localized mainly to a narrow pericellular zone. With progression into old age, this layer becomes less distinct, especially in areas of obvious mechanical attrition. Interestingly, individual laminin subunits were located in different zones of the cartilage, with laminin α1 showing preferential localization around a select population of superficial layer chondrocytes. We propose that the chondrocyte, like several other cell types of mesenchymal origin, is surrounded by the functional equivalent of a basement membrane. This structure is presumably involved in maintaining chondrocyte phenotype and viability and may well allow a new understanding of cartilage development and provide clues to the progression of degenerative joint disorders.
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| 7. |
- Salmivirta, K, et al.
(author)
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Binding of mouse nidogen-2 to basement membrane components and cells and its expression in embryonic and adult tissues suggest complementary functions of the two nidogens
- 2002
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In: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 279:2, s. 188-201
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Journal article (peer-reviewed)abstract
- Nidogen-1 binds several basement membrane components by well-defined, domain-specific interactions. Organ culture and gene targeting approaches suggest that a high-affinity nidogen-binding site of the laminin gamma1 chain (y1III4) is important for kidney development and for nerve guidance. Other proteins may also bind gamma1III4, although human nidogen-2 binds poorly to the mouse laminin gamma1 chain. We therefore characterized recombinant mouse nidogen-2 and its binding to basement membrane proteins and cells. Mouse nidogen-1 and -2 interacted at comparable levels with collagen IV, perlecan, and fibulin-2 and, most notably, also with laminin-1 fragments P1 and gamma1III3-5, which both contain the gamma1III4 module. In embryos, nidogen-2 mRNA was produced by mesenchyme at sites of epithelial-mesenchymal interactions, but the protein was deposited on epithelial basement membranes, as previously shown for nidogen-1. Hence, binding of both nidogens to the epithelial laminin gamma1 chain is dependent on epithelial-mesenchymal interactions. Epidermal growth factor stimulated expression of both nidogens in embryonic submandibular glands. Both nidogens were found in all studied embryonic and adult basement membranes. Nidogen-2 was more adhesive than nidogen-1 for some cell lines and was mainly mediated by alpha3beta1 and alpha6beta1 integrins as shown by antibody inhibition. These findings revealed extensive coregulation of nidogen-1 and -2 expression and much more complementary functions of the two nidogens than previously recognized. (C) 2002 Elsevier Science (USA).
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| 8. |
- Schéele, Susanne, et al.
(author)
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Laminin isoforms in development and disease.
- 2007
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In: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 85:8, s. 825-836
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Research review (peer-reviewed)abstract
- The members of the laminin family of heterotrimers are major constituents of all basement membranes, sheet-like extracellular structures, present in almost all organs. The laminins bind to cell surface receptors and thereby tightly connect the basement membrane to the adjacent cell layer. This provides for the specific basement membrane functions to stabilize cellular structures, to serve as effective physical barriers, and furthermore, to govern cell fate by inducing intracellular signalling cascades. Many different types of diseases involve basement membranes and laminins. Metastasizing solid tumors must pass through basement membranes to reach the vascular system, and various microbes and viruses enter the cells through direct interaction with laminins. Furthermore, whereas mutations in one specific laminin chain lead to a muscular disorder, mutations of other laminin chains cause skin blistering and kidney defects, respectively. This review summarizes recent progress concerning the molecular mechanisms of laminins in development and disease. The current knowledge may lead to clinical treatment of lamininopathies and may include stem-cell approaches as well as gene therapy.
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| 9. |
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| 10. |
- Yu, Hao, et al.
(author)
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beta 1 Integrin and alpha-dystroglycan binding sites are localized to different laminin-G-domain-like (LG) modules within the laminin alpha 5 chain G domain
- 2003
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In: Biochemical Journal. - 0264-6021. ; 371, s. 289-299
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Journal article (peer-reviewed)abstract
- Laminins are a group of extracellular-matrix proteins important in development and disease. They are heterotrimers, and specific domains in the different chains have specialized functions. The G domain of the alpha5 chain has now been produced in transfected mammalian cells as single modules and two tandem arrays, alpha5LG1-3 and alpha5LG4-5 (LG is laminin G domain-like.). Using these fragments we produced specific polyclonal antibodies functional in immunoblotting and immunofluorescence studies and in solid-phase assays. Both alpha5LG tandem arrays had physiologically relevant affinities for sulphated ligands such as heparin and sulphatides. Cells adhered to these fragments and acquired a spread morphology when plated on a5LG1-3. Binding of integrins alpha3beta1 and alpha6beta1 was localized to the alpha5LG1-3 modules, and a-dystroglycan binding was localized to the a5LG4-5 modules, thus locating these activities to different LG modules within the laminin a5 G domain. However, both these activities were of relatively low affinity, indicating that integrin-mediated cell adhesion to the laminin 10/11 alpha5G domain depends on contributions from the other chains of the heterotrimer and that high-affinity a-dystroglycan binding could be dependent on specific Ca2+-ion-co-ordinating amino acids absent from alpha5LG4-5.
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