PMID: 9547338May 23, 1998Paper

Extent of laminin-5 assembly and secretion effect junctional epidermolysis bullosa phenotype

The Journal of Experimental Medicine
C MatsuiW K Hoeffler

Abstract

Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein-protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal miti...Continue Reading

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Citations

Nov 10, 2000·International Journal of Cancer. Journal International Du Cancer·I SordatB Sordat
Jun 5, 1999·Journal of Immunological Methods·S AmanoR E Burgeson
Jun 24, 1999·Journal of Dermatological Science·M F Jonkman
Jan 30, 2013·Toxicology and Applied Pharmacology·Yoke-Chen ChangDonald R Gerecke
Apr 28, 2005·Experimental Dermatology·Nobuko AkutsuToshio Nishiyama
Jun 15, 2005·Clinical and Experimental Dermatology·K J Hamill, W H I McLean
Dec 15, 2005·Advances in Dermatology·Josephine Chu McAllister, M Peter Marinkovich
Mar 25, 2000·The Journal of Investigative Dermatology·C K WangW K Hoeffler
Sep 19, 2001·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·K M HaasH Kosmehl
Feb 21, 2006·Journal of Applied Toxicology : JAT·Michael P ShakarjianDonald R Gerecke
Mar 4, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·R MittwollenJ Hammersen
Jun 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M G KimR H Schwartz

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