Tenascin-C inhibits β1 integrin-dependent cell adhesion and neurite outgrowth on fibronectin by a disialoganglioside-mediated signaling mechanism

被引:48
作者
Probstmeier, R
Pesheva, P
机构
[1] Univ Bonn, Dept Physiol Neurophysiol, D-53111 Berlin, Germany
[2] Univ Bonn, Inst Anim Anat & Physiol, D-53111 Berlin, Germany
关键词
beta(1) integrin; disialogangliosides; cell adhesion; fibronectin; tenascin-C;
D O I
10.1093/glycob/9.2.101
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have previously shown that the extracellular matrix molecule tenascin-C inhibits fibronectin-mediated cell adhesion and neurite outgrowth by an interaction with a cellular RGD-independent receptor which interferes with the adhesion and neurite outgrowth promoting activities of the fibronectin receptor(s), Here we demonstrate that the inhibitory effect of tenascin-C on beta(1) integrin-dependent cell adhesion and neurite outgrowth is mediated by the interaction of the protein with membrane-associated disialogangliosides, which interferes with protein kinase C-related signaling pathways. First, in substratum mixtures with fibronectin, an RGD sequence-containing fragment of the molecule or synthetic peptide, tenascin-C inhibited cell adhesion and spreading by a disialoganglioside-dependent, sialidase-sensitive mechanism leading to an inhibition of protein kinase C, Second, the interaction of intact or trypsinized, i,e,, cell surface glycoprotein-free, cells with immobilized tenascin-C was strongly inhibited by gangliosides or antibodies to gangliosides and tenascin-C, Third, preincubation of immobilized tenascin-C with soluble disialogangliosides resulted in a delayed cell detachment as a function of time. Similar to tenascin-C, immobilized antibody to GD2 (3F8) or sphingosine, a protein kinase C inhibitor, strongly inhibited RGD-dependent cell spreading. Finally the degree of tenascin-C-induced inhibition of cell adhesion was proportional to the degree of disialoganglioside levels of expression by different cells suggesting the relevance of such mechanism in modulating integrin-mediated cell-matrix interactions during pattern formation or tumor progression.
引用
收藏
页码:101 / 114
页数:14
相关论文
共 113 条
[1]  
ADAMS JC, 1993, DEVELOPMENT, V117, P1183
[2]  
AUKHIL I, 1993, J BIOL CHEM, V268, P2542
[3]  
Bambrick LL, 1996, J NEUROSCI RES, V46, P305, DOI 10.1002/(SICI)1097-4547(19961101)46:3<305::AID-JNR3>3.3.CO
[4]  
2-2
[5]  
Bannerman PG, 1996, J NEUROSCI RES, V45, P549
[6]  
BARTSCH S, 1992, J NEUROSCI, V12, P736
[7]  
BARTSCH U, 1994, J NEUROSCI, V14, P4756
[8]   IMMUNOHISTOLOGICAL LOCALIZATION OF TENASCIN IN THE DEVELOPING AND LESIONED ADULT-MOUSE OPTIC-NERVE [J].
BARTSCH, U ;
BARTSCH, S ;
DORRIES, U ;
SCHACHNER, M .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1992, 4 (04) :338-352
[9]  
BOZYCZKO D, 1986, J NEUROSCI, V6, P1241
[10]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3