title: Homotypic versican G1 domain interactions enhance hyaluronan incorporation into fibrillin microfibrils.
abstract: Versican G1 domain-containing fragments (VG1Fs) have been identified in extracts from the dermis in which hyaluronan (HA)-versican-fibrillin complexes are found. However, the molecular assembly of VG1Fs in the HA-versican-microfibril macrocomplex has not yet been elucidated. Here, we clarify the role of VG1Fs in the extracellular macrocomplex, specifically in mediating the recruitment of HA to microfibrils. Sequential extraction studies suggested that the VG1Fs were not associated with dermal elements through HA binding properties alone. Overlay analyses of dermal tissue sections using the recombinant versican G1 domain, rVN, showed that rVN deposited onto the elastic fiber network. In solid-phase binding assays, rVN bound to isolated nondegraded microfibrils. rVN specifically bound to authentic versican core protein produced by dermal fibroblasts. Furthermore, rVN bound to VG1Fs extracted from the dermis and to nondenatured versican but not to fibrillin-1. Homotypic binding of rVN was also seen. Consistent with these binding properties, macroaggregates containing VG1Fs were detected in high molecular weight fractions of sieved dermal extracts and visualized by electron microscopy, which revealed localization to microfibrils at the microscopic level. Importantly, exogenous rVN enhanced HA recruitment both to isolated microfibrils and to microfibrils in tissue sections in a dose-dependent manner. From these data, we propose that cleaved VG1Fs can be recaptured by microfibrils through VG1F homotypical interactions to enhance HA recruitment to microfibrils.
authors: From the Department of Advanced Medicine and.
authors: Yusuke
authors: Y
authors: Murasawa
authors: Ken
authors: K
authors: Watanabe
authors: Masahiko
authors: M
authors: Yoneda
authors: Masahiro
authors: M
authors: Zako
authors: Koji
authors: K
authors: Kimata
authors: Lynn Y
authors: LY
authors: Sakai
authors: Zenzo
authors: Z
authors: Isogai
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D020405:Dermis / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D004548:Elasticity / Q000187:drug effects; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008024:Ligands; D008297:Male; D020894:Microfibrils / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014020:Tissue Extracts; D053675:Versicans / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D054392:Adipokines
chemical_list: D000906:Antibodies; D000071838:Fibrillin-1; D000071837:Fibrillins; D006820:Hyaluronic Acid; D008024:Ligands; D008840:Microfilament Proteins; D010455:Peptides; D011994:Recombinant Proteins; D014020:Tissue Extracts; D053675:Versicans; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: ADAM ADAMTS; Dermis; Extracellular Matrix; Fibrillin; Hyaluronate; Proteoglycan; Versican
references: EMBO J. 1989 Oct;8(10):2975-81
references: 2583089
references: J Biol Chem. 1994 Jul 22;269(29):19116-22
references: 8034670
references: J Biol Chem. 2006 Apr 14;281(15):10381-8
references: 16469746
references: J Biol Chem. 2011 Sep 30;286(39):34298-310
references: 21828051
references: J Cell Biol. 1994 Mar;124(5):817-25
references: 8120102
references: J Biol Chem. 1986 Oct 15;261(29):13517-25
references: 3759975
references: Development. 2010 Dec;137(23):4029-38
references: 21041365
references: Exp Cell Res. 2008 Dec 10;314(20):3638-53
references: 18845143
references: Cancer Res. 1996 Sep 1;56(17):3902-8
references: 8752156
references: J Biol Chem. 2009 Jun 19;284(25):16872-16881
references: 19349279
references: J Biol Chem. 2005 Feb 18;280(7):5435-48
references: 15590670
references: J Biol Chem. 1999 Jul 16;274(29):20444-9
references: 10400671
references: J Biol Chem. 2010 Aug 6;285(32):24943-55
references: 20529844
references: J Invest Dermatol. 2007 Jul;127(7):1657-63
references: 17363913
references: J Biol Chem. 1963 Feb;238:622-7
references: 14023808
references: J Histochem Cytochem. 1991 Apr;39(4):441-9
references: 2005373
references: Anat Embryol (Berl). 1999 Jan;199(1):45-56
references: 9924934
references: J Biol Chem. 1986 Aug 25;261(24):11429-36
references: 3015971
references: J Biol Chem. 2004 Mar 26;279(13):12060-6
references: 14724283
references: J Biol Chem. 2003 Oct 24;278(43):42330-9
references: 12907688
references: J Biol Chem. 2003 Oct 17;278(42):41205-12
references: 12888576
references: J Biol Chem. 2009 Nov 13;284(46):31493-7
references: 19734141
references: J Histochem Cytochem. 1996 Apr;44(4):303-12
references: 8601689
references: Lab Invest. 1995 Jun;72(6):662-9
references: 7783424
references: J Biol Chem. 2001 Apr 20;276(16):13372-8
references: 11278559
references: FASEB J. 2004 Apr;18(6):779-81
references: 14977887
references: J Biol Chem. 2002 Feb 15;277(7):4585-8
references: 11717315
references: J Biochem. 1998 Oct;124(4):687-93
references: 9756610
references: Dev Cell. 2009 Nov;17(5):687-98
references: 19922873
references: Matrix Biol. 2000 Nov;19(6):457-70
references: 11068200
references: J Cell Biol. 1986 Dec;103(6 Pt 1):2499-509
references: 3536967
references: J Biol Chem. 1989 Apr 5;264(10):5981-7
references: 2466833
references: Glycobiology. 2011 Feb;21(2):257-68
references: 20947661
references: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2870-7
references: 18390636
references: Dev Cell. 2009 Nov;17(5):584-6
references: 19922863
references: J Biol Chem. 2002 Feb 8;277(6):4565-72
references: 11726670
references: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9748-53
references: 8790402
references: J Biol Chem. 1985 Oct 15;260(23):12402-4
references: 3900075
references: J Biol Chem. 1996 Aug 9;271(32):19489-96
references: 8702639
references: J Biol Chem. 1992 May 15;267(14):10003-10
references: 1577773
references: J Biol Chem. 2007 Feb 9;282(6):4007-20
references: 17158461
references: Nat Genet. 1997 Oct;17(2):218-22
references: 9326947
references: J Biol Chem. 2001 Jan 12;276(2):1253-61
references: 11038354
references: J Histochem Cytochem. 2009 Sep;57(9):889-97
references: 19506088
references: J Biol Chem. 2003 Jan 24;278(4):2750-7
references: 12429738