title: Leda-1/Pianp is targeted to the basolateral plasma membrane by a distinct intracellular juxtamembrane region and modulates barrier properties and E-Cadherin processing.
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.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Evdokimov
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Siladitta
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schledzewski
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gorzelanny
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University and Center of Excellence in Dermatology, Mannheim, Germany.
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.affiliation: 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.
authors.forename: Cyrill
authors.initials: C
authors.lastname: Géraud
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D009419:Nerve Tissue Proteins; C557210:PIANP protein, human; D053829:Amyloid Precursor Protein Secretases
keywords: Cell junction; E-Cadherin; Intramembrane proteolysis; Shedding; Transepithelial barrier