Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion.
Syndecan-4 is a membrane-bound heparan sulfate proteoglycan that participates in cell-cell and cell-matrix interactions and modulates adhesion and migration of many cell types. Through its extracellular domain, syndecan-4 cooperates with adhesion molecules and binds matrix components relevant for cell migration. Importantly, syndecan-4 is a substrate of extracellular proteases, however the biological significance of this cleavage has not been elucidated. Here, we show that the secreted metalloprotease ADAMTS1, involved in angiogenesis and inflammatory processes, cleaves the ectodomain of syndecan-4. We further showed that this cleavage results in altered distribution of cytoskeleton components, functional loss of adhesion, and gain of migratory capacities. Using syndecan-4 null cells, we observed that ADAMTS1 proteolytic action mimics the outcome of genetic deletion of this proteoglycan with regards to focal adhesion. Our findings suggest that the shedding of syndecan-4 by ADAMTS1 disrupts cell adhesion and promotes cell migration.
Rodríguez-Manzaneque
Juan Carlos
JC
Medical Oncology Research Program, Vall d'Hebron University Hospital Research Institute/Universidad Autónoma de Barcelona, Barcelona 08035, Spain. juancarlos.rodriguez@genyo.es
Carpizo
Darren
D
Plaza-Calonge
María del Carmen
Mdel C
Torres-Collado
Antoni Xavier
AX
Thai
Shelley N-M
SN
Simons
Michael
M
Horowitz
Arie
A
Iruela-Arispe
M Luisa
ML
D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D022001:Focal Adhesions / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D053671:Syndecan-4 / Q000378:metabolism*; D014162:Transfection
D000199:Actins; D006025:Glycosaminoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508304:SDC4 protein, human; D053671:Syndecan-4; D045726:Metalloproteases; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein
Chem Rev. 2002 Dec;102(12):4627-38
12475204
Mol Cell Neurosci. 2005 May;29(1):82-96
15866049
Cell. 2002 Nov 27;111(5):635-46
12464176
J Biol Chem. 1998 May 8;273(19):11563-9
9565572
EMBO J. 2006 Nov 15;25(22):5270-83
17082774
Proc Natl Acad Sci U S A. 1985 May;82(10):3197-201
3858816
J Clin Invest. 2001 Jan;107(2):R9-R14
11160142
EMBO J. 1999 Feb 1;18(3):578-85
9927417
J Biol Chem. 2003 Dec 19;278(51):51340-6
14534304
Nat Rev Mol Cell Biol. 2003 Dec;4(12):926-37
14685171
J Cell Biol. 2002 May 13;157(4):715-25
12011116
J Biol Chem. 2001 Dec 14;276(50):47483-8
11585825
J Biol Chem. 2006 Jun 30;281(26):17827-37
16641089
J Biol Chem. 2002 Sep 6;277(36):32970-7
12087088
Biochem Biophys Res Commun. 2002 Apr 26;293(1):501-8
12054629
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2805-10
10077592
J Biol Chem. 1998 May 29;273(22):13912-7
9593739
J Cell Sci. 1999 Oct;112 ( Pt 20):3421-31
10504291
Nat Rev Cancer. 2002 Jul;2(7):521-8
12094238
J Biol Chem. 2000 Aug 18;275(33):25791-7
10827174
J Biol Chem. 1994 Aug 19;269(33):21204-14
7520439
Dev Dyn. 2000 Dec;219(4):539-44
11084653
Biochem J. 2005 Feb 15;386(Pt 1):15-27
15554875
Circ Res. 2005 Mar 18;96(5):488-500
15774861
Nat Rev Mol Cell Biol. 2005 Jul;6(7):530-41
16072037
Oncogene. 2006 Apr 20;25(17):2452-67
16314835
J Biol Chem. 2003 Mar 14;278(11):9576-84
12509413
J Biol Chem. 2000 Oct 27;275(43):33471-9
10944521
J Biol Chem. 2005 Oct 14;280(41):34441-6
16087677
J Biol Chem. 2007 Feb 2;282(5):3221-30
17130131
J Cell Biol. 2000 Feb 21;148(4):811-24
10684261
Mol Biol Cell. 1994 Jul;5(7):797-805
7812048
J Biol Chem. 1997 Jun 6;272(23):14713-20
9169435
J Biol Chem. 2003 Oct 17;278(42):40764-70
12904296
Cell. 2004 Jan 23;116(2):167-79
14744429
J Clin Invest. 2001 Aug;108(3):349-55
11489925
J Biol Chem. 1997 May 16;272(20):12901-4
9148893
J Biol Chem. 2005 Jun 24;280(25):23844-52
15843381
Nature. 2007 Apr 26;446(7139):1030-7
17460664
Glycoconj J. 2002 May-Jun;19(4-5):305-13
12975609
Cell. 1997 Nov 14;91(4):439-42
9390552
Lab Invest. 2001 Apr;81(4):509-16
11304570
Int J Biochem Cell Biol. 2007;39(3):505-28
17097330