title: Targeting of EMILIN-1 and EMILIN-2 to Fibrillin Microfibrils Facilitates their Incorporation into the Extracellular Matrix.
abstract: Elastin microfibril interface-located proteins (EMILINs) 1 and 2 belong to a family of structurally related extracellular glycoproteins with unique functions in the extracellular space, such as modulation of pro-transforming growth factor-β processing, activation of the extrinsic apoptotic pathway, and regulation of Hedgehog and Wnt ligand bioavailability. However, little is known about how EMILINs may exert their extracellular functions. We therefore investigated the spatiotemporal localization and deposition of EMILIN-1 and -2 within the extracellular space. By using immunoelectron and immunofluorescence microscopy together with biochemical extraction, we showed that EMILIN-1 and -2 are targeted to fibrillin microfibrils in the skin. In addition, during skin wound healing and in vitro matrix fiber assembly by primary dermal fibroblasts, EMILIN-1 and -2 are deposited on and coregulated with fibrillin. Analysis of wounds and mouse embryonic fibroblast cultures showed that EMILIN-1 and -2 network formation also requires the presence of fibronectin. Disruption of microfibrils in fibrillin-1-deficient mice leads to fragmentation of the EMILIN-1 and -2 networks, suggesting an involvement of EMILINs in fibrillin-related skin disorders. The addition of EMILINs to the ligand repertoire of fibrillin strengthens the concept of fibrillin microfibrils as extracellular scaffolds integrating cellular force transmission and growth factor bioactivity.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Alvise
authors.initials: A
authors.lastname: Schiavinato
authors.affiliation: Shriners Hospital for Children, Portland, Oregon, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Wohl
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Corallo
authors.affiliation: Experimental Oncology 2, CRO, IRCCS, National Cancer Institute, Aviano, PN, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Wagener
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. Electronic address: gsengle@uni-koeln.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Sengle
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D000071838:Fibrillin-1 / Q000235:genetics; D000071837:Fibrillins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000293:injuries; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000473:pathology*; D054392:Adipokines
chemical_list: D015415:Biomarkers; D000071838:Fibrillin-1; D000071837:Fibrillins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C486064:Emilin2 protein, mouse; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C030340:elastin microfibril interface located protein