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Biochem Biophys Res Commun. 2016 Jul 8;475(4):342-9. doi: 10.1016/j.bbrc.2016.05.092. Epub 2016 May 20.

Leda-1/Pianp is targeted to the basolateral plasma membrane by a distinct intracellular juxtamembrane region and modulates barrier properties and E-Cadherin processing.

Author information

1
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
2
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany. Electronic address: cyrill.geraud@umm.de.

Abstract

Leda-1/Pianp is a type-I transmembrane protein which is sorted to the basolateral membrane domain of polarized epithelial cells. Here, we investigated trafficking mechanisms and functions of Leda-1/Pianp in MDCK and MCF-7 cells. Basolateral sorting and posttranslational modifications depended on the intracellular juxtamembrane region. Functionally, Leda-1/Pianp increased the transepithelial electrical resistance generated by a polarized cell sheet. Furthermore, resistance to junctional destabilization by tumor cells was enhanced by Leda-1/Pianp indicating increased stability and tightness of intercellular junctions. While Claudin 1 and 4 expression and activities of small GTPases were not affected, γ-Secretase-mediated cleavage of E-Cadherin was attenuated by Leda-1/Pianp. Regulation of proteolytic processing is thus a molecular mechanism by which Leda-1/Pianp can affect junctional integrity and function.

KEYWORDS:

Cell junction; E-Cadherin; Intramembrane proteolysis; Shedding; Transepithelial barrier

PMID:
27216462
DOI:
10.1016/j.bbrc.2016.05.092
[Indexed for MEDLINE]

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