title: A study on the interactions between heparan sulfate proteoglycans and Wnt proteins.
abstract: The Wnt signaling pathway plays key roles in development and adult homeostasis. Wnt proteins are secreted, lipid-modified glycoproteins. They can form morphogen gradients that are regulated at the level of protein secretion, diffusion, and internalization. These gradients can only exist if the hydrophobic Wnt proteins are prevented from aggregating in the extracellular environment. Heparan sulfate proteoglycans (HSPGs) are necessary for proper activity of Wnt proteins and influence their distribution along the morphogenetic gradient. In this study, we show that HSPGs are able to maintain the solubility of Wnt proteins, thus stabilizing their signaling activity. Our results suggest that the role of HSPGs is not only to concentrate Wnt molecules at the cell surface but also to prevent them from aggregating in the extracellular environment.
authors.affiliation: Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fuerer
authors.forename: Shukry J
authors.initials: SJ
authors.lastname: Habib
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D008156:Luciferases; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D001616:beta-Galactosidase
chemical_list: D019812:Heparan Sulfate Proteoglycans; D051153:Wnt Proteins; D060508:Wnt3 Protein; D008156:Luciferases; D001616:beta-Galactosidase
references.citation: Dev Biol. 2008 Aug 15;320(2):436-45
references.pmid: 18617162
references.citation: Chem Rev. 2005 Jul;105(7):2745-64
references.pmid: 16011323
references.citation: Curr Opin Cell Biol. 2008 Apr;20(2):119-25
references.pmid: 18339531
references.citation: Dev Cell. 2008 May;14(5):712-25
references.pmid: 18477454
references.citation: Development. 1999 Mar;126(6):1211-23
references.pmid: 10021340
references.citation: Cell. 1990 Sep 21;62(6):1073-85
references.pmid: 2205396
references.citation: Dev Cell. 2007 Jul;13(1):57-71
references.pmid: 17609110
references.citation: Nat Cell Biol. 2006 May;8(5):492-500
references.pmid: 16604063
references.citation: Development. 2001 Jan;128(1):87-94
references.pmid: 11092814
references.citation: Nature. 1999 Jul 15;400(6741):281-4
references.pmid: 10421372
references.citation: EMBO J. 1985 Apr;4(4):905-12
references.pmid: 3160583
references.citation: J Biol Chem. 2005 Jan 21;280(3):2116-25
references.pmid: 15537637
references.citation: Cell. 2006 Nov 3;127(3):469-80
references.pmid: 17081971
references.citation: Traffic. 2009 Mar;10(3):334-43
references.pmid: 19207483
references.citation: Dev Cell. 2001 Aug;1(2):251-64
references.pmid: 11702784
references.citation: Annu Rev Biochem. 1999;68:729-77
references.pmid: 10872465
references.citation: Science. 2001 Aug 31;293(5535):1663-6
references.pmid: 11533491
references.citation: Nature. 2003 May 22;423(6938):448-52
references.pmid: 12717451
references.citation: Development. 2004 Apr;131(7):1563-75
references.pmid: 14998928
references.citation: Cell. 2005 Mar 25;120(6):857-71
references.pmid: 15797385
references.citation: Development. 1997 Aug;124(16):3055-64
references.pmid: 9272947
references.citation: Methods Mol Biol. 2008;468:17-29
references.pmid: 19099243
references.citation: Nature. 1990 Aug 30;346(6287):847-50
references.pmid: 2202907
references.citation: Development. 1997 Jul;124(13):2623-32
references.pmid: 9217004
references.citation: Development. 2004 May;131(9):1927-38
references.pmid: 15056609
references.citation: BMC Cell Biol. 2006 Jul 06;7:28
references.pmid: 16824228
references.citation: Dev Cell. 2006 Dec;11(6):791-801
references.pmid: 17141155
references.citation: Nature. 2005 May 5;435(7038):58-65
references.pmid: 15875013
references.citation: Curr Biol. 2003 Apr 15;13(8):680-5
references.pmid: 12699626
references.citation: Curr Biol. 2002 Jun 4;12(11):957-62
references.pmid: 12062063
references.citation: Nature. 1999 Jul 15;400(6741):276-80
references.pmid: 10421371
references.citation: Development. 1994 Sep;120(9):2703-11
references.pmid: 7956842
references.citation: Development. 2004 Jan;131(1):73-82
references.pmid: 14645127
references.citation: Nat Genet. 1999 Aug;22(4):361-5
references.pmid: 10431240
references.citation: J Cell Biol. 2003 Jul 21;162(2):341-51
references.pmid: 12860968
references.citation: Development. 1997 Sep;124(18):3565-73
references.pmid: 9342049
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14700-5
references.pmid: 17804805
references.citation: Dev Cell. 2004 Oct;7(4):513-23
references.pmid: 15469840
references.citation: Curr Biol. 2000 Mar 23;10(6):293-300
references.pmid: 10744972