Universität zu Köln

Rietscher, Katrin, Wolf, Annika, Hause, Gerd, Rother, Annekatrin, Keil, Rene, Magin, Thomas M., Glass, Markus ORCID: 0000-0003-2718-8907, Niessen, Carien M. and Hatzfeld, Mechthild (2016). Growth Retardation, Loss of Desmosomal Adhesion, and Impaired Tight Junction Function Identify a Unique Role of Plakophilin 1 In Vivo. J. Invest. Dermatol., 136 (7). S. 1471 - 1479. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Desmosomes mediate strong intercellular adhesion through desmosomal cadherins that interact with intracellular linker proteins including plakophilins (PKPs) 1-3 to anchor the intermediate filaments. PKPs show overlapping but distinct expression patterns in the epidermis. So far, the contribution of individual PKPs in differentially regulating desmosome function is incompletely understood. To resolve the role of PKP1 we ablated the PKP1 gene. Here, we report that PKP1(-/-) mice were born at the expected mendelian ratio with reduced birth weight, but they otherwise appeared normal immediately after birth. However, their condition rapidly declined, and the mice died within 24 hours, developing fragile skin with lesions in the absence of obvious mechanical trauma. This was accompanied by sparse and small desmosomes. Newborn PKP1(-/-) mice showed disturbed tight junctions with an impaired inside-out barrier, whereas the outside-in barrier was unaffected. Keratinocytes isolated from these mice showed strongly reduced intercellular cohesion, delayed tight junction formation, and reduced transepithelial resistance and reduced proliferation rates. Our study shows a nonredundant and essential role of PKP1 in desmosome and tight junction function and supports a role of PKP1 in growth control, a function that is crucial in wound healing and epidermal carcinogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rietscher, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Hause, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Rother, Annekatrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Keil, Rene UNSPECIFIED UNSPECIFIED UNSPECIFIED Magin, Thomas M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Glass, Markus UNSPECIFIED orcid.org/0000-0003-2718-8907 UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatzfeld, Mechthild UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-271123
DOI:	10.1016/j.jid.2016.03.021
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	136
Number:	7
Page Range:	S. 1471 - 1479
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SKIN FRAGILITY; BARRIER FUNCTION; BETA-CATENIN; MUTATIONS; DESMOPLAKIN; PROTEIN; PLAKOGLOBIN; DEFECTS; PKP1; MORPHOGENESIS Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27112