Laminin 332 in Junctional Epidermolysis and as an Autoantigen in Mucous Membrane Pemphigoid

Published on Jan 1, 2015
· DOI :10.1007/978-3-662-45698-9_9
Patricia Rousselle46
Estimated H-index: 46
(CNRS: Centre national de la recherche scientifique),
Anna Michopoulou5
Estimated H-index: 5
(CNRS: Centre national de la recherche scientifique)
Sources
Abstract
Laminin 332, with chain composition α3, β3, γ2, is a component of basement membranes localised beneath specialised epithelia with secretory or protective function. This protein plays a pivotal structural role as it directly connects basal epithelial cells to the underlying extracellular matrix molecular networks. Its deficiency in human inherited and autoimmune disorders has emphasised the importance of laminin 332 for the structural integrity of the dermal–epidermal junction in skin. The junctional form of epidermolysis bullosa, a skin disease characterised by loss of cohesion between the epidermis and the dermis that results in blister formation and chronic wounds, is caused by genetic mutations in several different genes encoding proteins of the epidermal adhesion complex such as the three chains of laminin 332. Besides, autoimmune disorders affecting laminin 332 belong to the mucous membrane pemphigoid heterogeneous group of rare autoimmune blistering diseases. Anti-laminin 332 autoantibodies cause erosive lesions followed by scarring of the skin and mucous membranes. This chapter reviews the molecular characteristics of laminin 332, its organisation within basement membranes and its involvement in bullous diseases.
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References117
Newest
#1Philippe Bernard (URCA: University of Reims Champagne-Ardenne)H-Index: 15
#2Frank AntonicelliH-Index: 24
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Importance A rare variant of mucous membrane pemphigoid (MMP) is characterized by circulating anti–laminin 332 (Lam332) autoantibodies and seems to be associated with concurrent malignant neoplasms. Objective To determine the prevalence and clinical significance of anti-Lam332 autoantibody detection from a large series of patients with MMP. Design Multicenter retrospective study. Setting Four French national centers for autoimmune bullous diseases. Participants One hundred fifty-four patients wi...
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#1Patricia Rousselle (University of Lyon)H-Index: 46
#2Konrad Beck (Cardiff University)H-Index: 35
Laminin 332, composed of the α3, β3 and γ2 chains, is an epithelial-basement membrane specific laminin variant. Its main role in normal tissues is the maintenance of epithelial-mesenchymal cohesion in tissues exposed to external forces, including skin and stratified squamous mucosa. After being secreted and deposited in the extracellular matrix, laminin 332 undergoes physiological maturation processes consisting in the proteolytic processing of domains located within the α3 and the γ2 chains. Th...
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#1Erhard Hohenester (ICL: Imperial College London)H-Index: 61
#2Peter D. Yurchenco (RU: Rutgers University)H-Index: 69
The heterotrimeric laminins are a defining component of all basement membranes and self-assemble into a cell-associated network. The three short arms of the cross-shaped laminin molecule form the network nodes, with a strict requirement for one α, one β and one γ arm. The globular domain at the end of the long arm binds to cellular receptors, including integrins, α-dystroglycan, heparan sulfates and sulfated glycolipids. Collateral anchorage of the laminin network is provided by the proteoglycan...
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Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the α, β and γ chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically brid...
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#1Dimitra Kiritsi (University of Freiburg)H-Index: 23
#2Cristina HasH-Index: 36
Last. Leena Bruckner-TudermanH-Index: 65
view all 3 authors...
Laminin 332 is an essential component of the dermal-epidermal junction, a highly specialized basement membrane zone that attaches the epidermis to the dermis and thereby provides skin integrity and resistance to external mechanical forces. Mutations in the LAMA3, LAMB3 and LAMC2 genes that encode the three constituent polypeptide chains, α3, β3 and γ2, abrogate or perturb the functions of laminin 332. The phenotypic consequences are diminished dermal-epidermal adhesion and, as clinical symptoms,...
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#1Sonia Carulli (University of Lyon)H-Index: 2
#2Konrad BeckH-Index: 35
Last. Patricia RousselleH-Index: 46
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Keratinocyte migration during epidermal repair depends on interactions between cellular heparan sulfate proteoglycan receptors, syndecan-1 and -4, and the C-terminal globular domains (LG45) of the extracellular matrix protein laminin 332. This study investigates the molecular basis of the binding specificity of the syndecan-1 and -4 receptors expressed by human keratinocytes. We used site-directed mutagenesis to alter a recombinant LG45 protein by substituting the most critical basic residues wi...
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#1Kana MasunagaH-Index: 2
#2Mito ToyodaH-Index: 2
Last. Masutaka Furue (Kyushu University)H-Index: 67
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Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Substrate-bound laminin-332 specifically suppressed one type of mechanosensitive current (rapid...
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#1A. Shadi Kourosh (UTSW: University of Texas Southwestern Medical Center)H-Index: 2
#2Kim B. YanceyH-Index: 54
Mucous membrane pemphigoid (MMP) is the clinical phenotype of a group of autoimmune blistering diseases characterized by autoantibodies directed against different structural proteins in epidermal basement membranes. The clinical course and prognosis of MMP are affected by the specific autoantigen targeted, the titer and bioactivity profile of corresponding autoantibodies, and the specific mucosal sites of disease activity. Irreversible scarring and loss of function must be prevented by early dia...
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#1Dimitra Kiritsi (University Medical Center Freiburg)H-Index: 23
#2Johannes S. Kern (University Medical Center Freiburg)H-Index: 22
Last. Leena Bruckner-Tuderman (University Medical Center Freiburg)H-Index: 65
view all 6 authors...
Background Junctional epidermolysis bullosa (JEB), a group of hereditary skin fragility disorders, is associated with a wide variety of phenotypes, although all forms are characterised by trauma induced skin blistering and tissue separation at the dermal–epidermal junction zone. A subgroup, coined JEB-other, is associated with mutations in the COL17A1 gene encoding collagen XVII or, more rarely, with mutations in the laminin 332 genes LAMA3 , LAMB3 , or LAMC2 . The objective of this study is com...
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Cited By1
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#1Eva Roig-Rosello (University of Lyon)H-Index: 1
One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal junction-a complex network of extracellular matrix macromolecules that connect the outer epidermal layer to the underlying dermis. This junction provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behavior. It displays a distinctive microarchitecture characterized by a...
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