Heparin II Domain of Fibronectin Mediates Contractility Through an Alpha4beta1 Co-signaling Pathway

Overview

Journal Exp Cell Res

Specialty Cell Biology

Date 2010 Mar 23

PMID 20302860

Citations 21

Authors

Marie K Schwinn

Jose M Gonzalez Jr

BAnn T Gabelt

Nader Sheibani

Paul L Kaufman

Donna M Peters

Affiliations

Soon will be listed here.

Abstract

In the trabecular meshwork (TM) of the eye, regulation of tissue contractility by the PPRARI sequence within the Heparin II (HepII) domain of fibronectin is believed to control the movement of aqueous humor and dictate the level of intraocular pressure. This study shows that the HepII domain utilizes activated alpha4beta1 integrin and collagen to mediate a co-signaling pathway that down-regulates contractility in TM cells. siRNA silencing of alpha4beta1 integrin blocked the actin disrupting effects of both PPRARI and the HepII domain. The down-regulation of the actin cytoskeleton and contractility did not involve syndecan-4 or other heparan sulfate proteoglycans (HSPGs) since siRNA silencing of syndecan-4 expression or heparitinase removal of cell surface HSPGs did not prevent the HepII-mediated disruption of the actin cytoskeleton. HepII-mediated disruption of the cytoskeleton depended upon the presence of collagen in the extracellular matrix, and cell binding studies indicated that HepII signaling involved cross-talk between alpha4beta1 and alpha1/alpha2beta1 integrins. This is the first time that the PPRARI sequence in the HepII domain has been shown to serve as a physiological alpha4beta1 ligand, suggesting that alpha4beta1 integrin may be a key regulator of tissue contractility.

Citing Articles

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References

Rose D . The role of the alpha4 integrin-paxillin interaction in regulating leukocyte trafficking. Exp Mol Med. 2006; 38(3):191-5. DOI: 10.1038/emm.2006.23. View

Oh E, Woods A, Couchman J . Multimerization of the cytoplasmic domain of syndecan-4 is required for its ability to activate protein kinase C. J Biol Chem. 1997; 272(18):11805-11. DOI: 10.1074/jbc.272.18.11805. View

Bayless K, Meininger G, Scholtz J, Davis G . Osteopontin is a ligand for the alpha4beta1 integrin. J Cell Sci. 1998; 111 ( Pt 9):1165-74. DOI: 10.1242/jcs.111.9.1165. View

Porter J, Hogg N . Integrin cross talk: activation of lymphocyte function-associated antigen-1 on human T cells alters alpha4beta1- and alpha5beta1-mediated function. J Cell Biol. 1997; 138(6):1437-47. PMC: 2132554. DOI: 10.1083/jcb.138.6.1437. View

Mould A, Garratt A, Takada Y, Humphries M . Regulation of integrin function: evidence that bivalent-cation-induced conformational changes lead to the unmasking of ligand-binding sites within integrin alpha5 beta1. Biochem J. 1998; 331 ( Pt 3):821-8. PMC: 1219423. DOI: 10.1042/bj3310821. View

Rose D, Alon R, Ginsberg M . Integrin modulation and signaling in leukocyte adhesion and migration. Immunol Rev. 2007; 218:126-34. DOI: 10.1111/j.1600-065X.2007.00536.x. View

Hu Y, Gabelt B, Kaufman P . Monkey organ-cultured anterior segments: technique and response to H-7. Exp Eye Res. 2006; 82(6):1100-8. DOI: 10.1016/j.exer.2005.12.004. View

Liao Y, Gotwals P, Koteliansky V, Sheppard D, Van De Water L . The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem. 2002; 277(17):14467-74. DOI: 10.1074/jbc.M201100200. View

Barkalow F, Schwarzbauer J . Localization of the major heparin-binding site in fibronectin. J Biol Chem. 1991; 266(12):7812-8. View

10.

Elices M, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler M . VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990; 60(4):577-84. DOI: 10.1016/0092-8674(90)90661-w. View

11.

Hikita S, Cann G, Wingerd K, Mullick L, Wayne W, Webb S . Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons. Mol Cell Neurosci. 2003; 23(3):427-39. DOI: 10.1016/s1044-7431(03)00065-4. View

12.

Mostafavi-Pour Z, Askari J, Parkinson S, Parker P, Ng T, Humphries M . Integrin-specific signaling pathways controlling focal adhesion formation and cell migration. J Cell Biol. 2003; 161(1):155-67. PMC: 2172880. DOI: 10.1083/jcb.200210176. View

13.

Mould A, Humphries M . Identification of a novel recognition sequence for the integrin alpha 4 beta 1 in the COOH-terminal heparin-binding domain of fibronectin. EMBO J. 1991; 10(13):4089-95. PMC: 453158. DOI: 10.1002/j.1460-2075.1991.tb04985.x. View

14.

Iida J, Meijne A, Oegema Jr T, Yednock T, Kovach N, Furcht L . A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrin-mediated melanoma cell adhesion. J Biol Chem. 1998; 273(10):5955-62. DOI: 10.1074/jbc.273.10.5955. View

15.

Moyano J, Maqueda A, Casanova B, Garcia-Pardo A . Alpha4beta1 integrin/ligand interaction inhibits alpha5beta1-induced stress fibers and focal adhesions via down-regulation of RhoA and induces melanoma cell migration. Mol Biol Cell. 2003; 14(9):3699-715. PMC: 196561. DOI: 10.1091/mbc.e02-10-0667. View

16.

Sanka K, Maddala R, Epstein D, Rao P . Influence of actin cytoskeletal integrity on matrix metalloproteinase-2 activation in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2007; 48(5):2105-14. DOI: 10.1167/iovs.06-1089. View

17.

Humphries D, Silbert J . Chlorate: a reversible inhibitor of proteoglycan sulfation. Biochem Biophys Res Commun. 1988; 154(1):365-71. DOI: 10.1016/0006-291x(88)90694-8. View

18.

Duplaa C, Couffinhal T, Dufourcq P, Llanas B, Moreau C, Bonnet J . The integrin very late antigen-4 is expressed in human smooth muscle cell. Involvement of alpha 4 and vascular cell adhesion molecule-1 during smooth muscle cell differentiation. Circ Res. 1997; 80(2):159-69. DOI: 10.1161/01.res.80.2.159. View

19.

Woods A, McCarthy J, Furcht L, Couchman J . A synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. Mol Biol Cell. 1993; 4(6):605-13. PMC: 300967. DOI: 10.1091/mbc.4.6.605. View

20.

Xie Y, Sakatsume M, Nishi S, Narita I, Arakawa M, Gejyo F . Expression, roles, receptors, and regulation of osteopontin in the kidney. Kidney Int. 2001; 60(5):1645-57. DOI: 10.1046/j.1523-1755.2001.00032.x. View