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
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.
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收藏
页码:1881 / 1891
页数:11
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