{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:06:43Z","timestamp":1790896003336,"version":"4.1.0"},"reference-count":71,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[1996,7,1]],"date-time":"1996-07-01T00:00:00Z","timestamp":836179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Junctional epidermolysis bullosa (JEB) comprises a group of inherited autosomal recessive blistering disorders characterized by dermo-epidermal separation through the lamina lucida of the basement membrane. We identified a patient with JEB associated with pyloric atresia (PA), in whom the integrin \u03b24 subunit was completely absent. At the ultrastructural level, the hemidesmosomes were reduced in number, appeared rudimentary and lacked a subbasal dense plate and frequently an inner attachment plaque. However, keratin filaments were still anchored to the cytoplasmic plaque of the hemidesmosome. Immunofluorescence analysis showed that the \u03b24 subunit was absent in the skin of the PA-JEB patient, whereas the \u03b16 subunit appeared to be normally distributed along the basement membrane zone, as were the other hemidesmosomal components BP230, BP180 and HD1. Furthermore, the \u03b13 and \u03b21 subunits were not only detected at the lateral membranes of basal cells in PA-JEB skin, as in normal skin, but also along the basement membrane zone. The few hemidesmosome-like structures found in cultured keratinocytes from the PA-JEB patient contained the hemidesmosomal components BP230, BP180 and HD1, but not the integrin \u03b16 subunit. Like \u03b13, this subunit was colocalized with vinculin in focal contacts at the ends of actin stress fibers. Immunoprecipitation analysis revealed that \u03b16 was associated with \u03b21 on PA-JEB keratinocytes, whereas normal human keratinocytes (NHKs) exclusively express \u03b16\u03b24 on their cell surface. The initial adhesion of PA-JEB and normal keratinocytes to laminin-1 and laminin-5, both ligands for \u03b16\u03b21 and \u03b16\u03b24, was similar. In migration assays, the PA-JEB keratinocytes were more motile on laminin-5 than normal keratinocytes. Our observations indicate that the integrin \u03b16\u03b24 plays a crucial role in the proper assembly of hemidesmosomes and in the stabilization of the dermal-epidermal junction. The fragility of the skin and the blistering in this patient appear to have been due to the deficiency of the integrin \u03b24 subunit, which results in the formation of too few and structurally abnormal hemidesmosomes.<\/jats:p>","DOI":"10.1242\/jcs.109.7.1695","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T16:38:34Z","timestamp":1619368714000},"page":"1695-1706","source":"Crossref","is-referenced-by-count":107,"title":["Deficiency of the integrin \u03b24 subunit in junctional epidermolysis bullosa with pyloric atresia: consequences for hemidesmosome formation and adhesion properties"],"prefix":"10.1242","volume":"109","author":[{"given":"Carien M.","family":"Niessen","sequence":"first","affiliation":[{"name":"1 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth M. H.","family":"van der Raaij-Helmer","sequence":"additional","affiliation":[{"name":"2 Division of Dermatology, Free University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther H. M.","family":"Hulsman","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"van der Neut","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel F.","family":"Jonkman","sequence":"additional","affiliation":[{"name":"3 Department of Dermatology, University Hospital Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnoud","family":"Sonnenberg","sequence":"additional","affiliation":[{"name":"1 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,7,1]]},"reference":[{"key":"2024010323550483500_JOCES_109_7_1695C1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ng0394-299","article-title":"Herlitz\u2019s junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the \u03b32 subunit of nicein\/kalinin (laminin-5)","volume":"6","author":"Aberdam","year":"1994","journal-title":"Nature Genet"},{"key":"2024010323550483500_JOCES_109_7_1695C2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1177\/43.7.7608519","article-title":"Fluorescence overlay antigen mapping of the epidermal basement membrane zone: III. 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