title: Transcytosis of IL-11 and Apical Redirection of gp130 Is Mediated by IL-11α Receptor.
abstract: Interleukin (IL)-11 signaling is involved in various processes, including epithelial intestinal cell regeneration and embryo implantation. IL-11 signaling is initiated upon binding of IL-11 to IL-11R1 or IL-11R2, two IL-11α-receptor splice variants, and gp130. Here, we show that IL-11 signaling via IL-11R1/2:gp130 complexes occurs on both the apical and basolateral sides of polarized cells, whereas IL-6 signaling via IL-6R:gp130 complexes is restricted to the basolateral side. We show that basolaterally supplied IL-11 is transported and released to the apical extracellular space via transcytosis in an IL-11R1-dependent manner. By contrast, IL-6R and IL-11R2 do not promote transcytosis. In addition, we show that transcytosis of IL-11 is dependent on the intracellular domain of IL-11R1 and that synthetic transfer of the intracellular domain of IL-11R1 to IL-6R promotes transcytosis of IL-6. Our data define IL-11R as a cytokine receptor with transcytotic activity by which IL-11 and IL-6:soluble IL-6R complexes are transported across cellular barriers.
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Monhasery
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Moll
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia; Department of Molecular and Translational Medicine, Monash University, Clayton, 3168 VIC, Australia.
authors.forename: Carly
authors.initials: C
authors.lastname: Cuman
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Franke
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lamertz
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nitz
authors.affiliation: Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Görg
authors.affiliation: Department of Molecular and Translational Medicine, Monash University, Clayton, 3168 VIC, Australia.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Institute of Biochemistry, Kiel University, Olshausenstrasse 40, 24098 Kiel, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lokau
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Floss
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Piekorz
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia; Department of Molecular and Translational Medicine, Monash University, Clayton, 3168 VIC, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Dimitriadis
authors.affiliation: Institute of Biochemistry, Kiel University, Olshausenstrasse 40, 24098 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany. Electronic address: jscheller@uni-duesseldorf.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology*; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D004285:Dogs; D010064:Embryo Implantation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D053702:Receptors, Interleukin-11 / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D057900:Transcytosis / Q000502:physiology*
chemical_list: D017370:Interleukin-11; D015850:Interleukin-6; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130
keywords: IL-11; IL-11R; IL-6; apical; basolateral; gp130; transcytosis