The L1 adhesion molecule is a cellular ligand for VLA-5

被引：129

作者：

Ruppert, M

Aigner, S

Hubbe, M

Yagita, H

Altevogt, P

机构：

[1] GERMAN CANC RES CTR, TUMOR IMMUNOL PROGRAMME, D-69120 HEIDELBERG, GERMANY

[2] JUNTENDO UNIV, SCH MED, DEPT IMMUNOL, TOKYO 113, JAPAN

来源：

JOURNAL OF CELL BIOLOGY | 1995年 / 131卷 / 06期

关键词：

D O I：

10.1083/jcb.131.6.1881

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The L1 adhesion molecule is a member of the immunoglobulin superfamily shared by neural and immune cells. In the nervous system L1 can mediate cell binding by a homophilic mechanism. To analyze its function on leukocytes we studied whether L1 could interact with integrins. Here we demonstrate that VLA-5, an RGD-specific fibronectin receptor on a wide variety of cell types, can bind to murine L1. Mouse ESb-MP cells expressing VLA-5 and L1 could be induced to aggregate in the presence of specific mAbs to CD24 (heat-stable antigen), a highly and heterogeneously glycosylated glycophosphatidylinositol-linked differentiation antigen of hematopoietic and neural cells. The aggregation was blocked by both mAbs to L1 and VLA-5, respectively. Aggregation was blocked also by a synthetic RGD-containing peptide derived from the Ig-domain VI of the L1 protein. ESb-MP subclones with low L1 expression could not aggregate. In heterotypic binding assays mouse bone marrow cells could adhere in an L1-dependent fashion to platelets that expressed VLA-5. Also purified L1 coated to polystyrene beads could bind to platelets. The binding of L1-beads was again inhibited by mAbs to L1 and VLA-5, by soluble L1 and the L1-RGD peptide in a dose-dependent manner. Thymocytes or human Nalm-6 tumor cells expressing VLA-5 could adhere to affinity-purified L1 and to the L1-derived RGD-containing peptide coated to glass slides. The adhesion was strongly enhanced in the presence of Mn2+-ions and blocked by mAbs to VLA5. We also demonstrate a direct L1-VLA-5 protein interaction. Our results suggest a novel binding pathway, in which the VLA-5 integrin binds to L1 on adjacent cells. Given its rapid downregulation on lymphocytes after induction of cell proliferation, L1 may be important in integrin-mediated and activation-regulated cell-cell interactions.

引用

页码：1881 / 1891

页数：11

共 88 条

[21]

Chang S., Rathjen F.G., Raper J.A., Extension of neurites on axons is impaired by antibodies against specific neural cell surface glycoproteins, J. Cell. Biol., 104, pp. 355-362, (1987)

[22]

Conforti G., Dominguez-Jimenez C., Zanetti A., Gimbrone M.A.J., Cremona O., Marchisio P.C., Dejana E., Human endothelial cells express integrin receptors on the luminal aspect of their membrane, Blood, 80, pp. 437-446, (1992)

[23]

Davis L.S., Oppenheimer-Marks N., Bednarczyk J.L., McIntyre B.W., Linsky P.E., Fibronectin promotes proliferation of naive and memory T cells by signalling through the VLA-4 and VLA-5 integrin molecules, J. Immunol., 145, pp. 785-793, (1990)

[24]

Doherty P., Williams E., Walsh F.S., A soluble chimeric form of the L1 glycoprotein stimulates neurite outgrowth, Neuron., 14, pp. 57-66, (1995)

[25]

Faull R.J., Kovach N.L., Harlan J.M., Ginsberg H., Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: Two mechanisms with divergent biological consequences, J. Exp. Med., 179, pp. 1307-1316, (1994)

[26]

Felsenfeld D.P., Hynes M.A., Skoler K.M., Furley A.J., Jessell T.M., TAG-1 can mediate homophilic binding, but neurite outgrowth on TAG-1 requires an L1-like molecule and beta1 integrins, Neuron., 12, pp. 675-690, (1994)

[27]

Fischer G., Kunemund V., Schachner M., Neurite outgrowth patterns in cerebellar microexplant cultures are affected by antibodies to the cell surface glycoprotein L1, J. Neurosci., 6, pp. 605-612, (1986)

[28]

Furley A.J., Morton S.B., Manalo D., Karagogeos D., Dodd J., Jessell T.M., The axonal glvcoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity, Cell, 61, pp. 157-170, (1990)

[29]

Giancotti F.G., Ruoslahti E., Elevated levels of α5β1 fibronectin receptors suppress the transformed phenotype of Chinese hamster ovary cells, Cell, 60, pp. 849-859, (1990)

[30]

Guan J.L., Hynes R.O., Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α4β1, Cell, 60, pp. 53-61, (1990)

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