HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 22, 18828-18835, June 1, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/22/18828    most recent M100381200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spirito, F. Articles by Meneguzzi, G. Search for Related Content PubMed PubMed Citation Articles by Spirito, F. Articles by Meneguzzi, G. Social Bookmarking                      What's this?

Reduced Expression of the Epithelial Adhesion Ligand Laminin 5 in the Skin Causes Intradermal Tissue Separation^*

Flavia Spirito, Stéphane Chavanas, Catherine Prost-Squarcioni^§, Leena Pulkkinen^¶, Sylvie Fraitag, Christine Bodemer, Jean-Paul Ortonne, and Guerrino Meneguzzi^**

From U385 INSERM, Faculté de Médecine, Avenue de Valombrose, 06107 Nice cedex 2, France, the ^§ Département d'Histologie, Embryologie, et Cytogénétique, Faculté de Médecine Lariboisière Saint Louis, 75730 Paris Cedex 15, France, the ^¶ Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, and  Service de Dermatologie, Hôpital Necker Enfants Malades, 75730 Paris Cedex 15 Paris, France

Laminin 5, the major keratinocyte adhesion ligand, is found in the lamina lucida subregion of the epidermal basement membrane of the skin, where it colocalizes with the anchoring filaments. Mutations in the genes encoding laminin 5 cause junctional epidermolysis bullosa, an inherited skin blistering disease characterized by abnormal hemidesmosomes and cleavage of the lamina lucida leading to epidermal detachment. In this work we describe the genetic basis of a new subtype of lethal inherited epidermolysis bullosa associated with reduced skin reactivity to laminin 5, presence of mature hemidesmosomes, and intradermal cleavage of the skin. The epidermolysis bullosa patients were heterozygous for a nonsense mutation (Q896X) and a splice site mutation (76410TG) in the gene (LAMC2) for the 2 chain of laminin 5. The nonsense mutation causes accelerated decay of the corresponding mRNA, while the splice site mutation results in maturation of a cryptic wild-type 2 mRNA leading to reduced expression of wild-type laminin 5. In vitro studies using the probands' keratinocytes showed that secretion of reduced amounts of functional laminin 5 in the patient, although permitting formation of hemidesmosomes, fail to restore efficient cell adhesion. Our results provide the first evidence that laminin 5 contributes to the firm adhesion of the epithelial basement membrane to the underlying stroma. They also show that a low expression level of laminin 5 induces assembly of mature hemidesmosomes in vivo but fails to assure a stable cohesion of the dermal-epidermal junction.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. Mydel, J. M. Shipley, T. L. Adair-Kirk, D. G. Kelley, T. J. Broekelmann, R. P. Mecham, and R. M. Senior Neutrophil Elastase Cleaves Laminin-332 (Laminin-5) Generating Peptides That Are Chemotactic for Neutrophils J. Biol. Chem., April 11, 2008; 283(15): 9513 - 9522. [Abstract] [Full Text] [PDF]

				W. H. I. McLean, A. D. Irvine, K. J. Hamill, N. V. Whittock, C. M. Coleman-Campbell, J. E. Mellerio, G. S. Ashton, P. J. H. Dopping-Hepenstal, R. A. J. Eady, T. Jamil, et al. An unusual N-terminal deletion of the laminin {alpha}3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome Hum. Mol. Genet., September 15, 2003; 12(18): 2395 - 2409. [Abstract] [Full Text] [PDF]