Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1.

Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1.
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DOI:
10.1083/jcb.200709019
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发表时间:
2008-03-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Nabi IR
Nabi IR
中科院分区:
其他
文献类型:
--
作者:
Goetz JG;Joshi B;Lajoie P;Strugnell SS;Scudamore T;Kojic LD;Nabi IR

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酪氨酸磷酸化的小窝蛋白-1(pY 14 Cav 1)和GlcNAc-转移酶V(Mgat 5)都与粘着斑(FA)有关;然而,它们在这种情况下的功能尚不清楚。在这里,我们表明,半乳糖凝集素-3结合Mgat 5-修饰的N-聚糖的功能与pY 14 Cav 1一起稳定FA内的粘着斑激酶(FAK),从而促进FA的拆卸和营业额。单独表达Mgat 5/半乳糖凝集素晶格诱导FA和细胞铺展。然而,FAK在FA中的稳定化也需要pY 14 Cav 1的表达。在缺乏Mgat 5/半乳糖凝集素晶格的细胞中,pY 14 Cav 1不足以促进FAK稳定、FA分解和周转。在人MDA-435癌细胞中,Cav 1的表达,而不是突变Y14 FCav 1,稳定FAK交换,并刺激从头FA形成在肿胀的细胞区域。因此,半乳糖凝集素晶格和pY 14 Cav 1之间的跨膜串扰通过稳定FA内的FAK来促进FA周转,从而定义了半乳糖凝集素-3和pY 14 Cav 1在肿瘤细胞迁移中先前未知的相互依赖的作用。
Both tyrosine-phosphorylated caveolin-1 (pY14Cav1) and GlcNAc-transferase V (Mgat5) are linked with focal adhesions (FAs); however, their function in this context is unknown. Here, we show that galectin-3 binding to Mgat5-modified N-glycans functions together with pY14Cav1 to stabilize focal adhesion kinase (FAK) within FAs, and thereby promotes FA disassembly and turnover. Expression of the Mgat5/galectin lattice alone induces FAs and cell spreading. However, FAK stabilization in FAs also requires expression of pY14Cav1. In cells lacking the Mgat5/galectin lattice, pY14Cav1 is not sufficient to promote FAK stabilization, FA disassembly, and turnover. In human MDA-435 cancer cells, Cav1 expression, but not mutant Y14FCav1, stabilizes FAK exchange and stimulates de novo FA formation in protrusive cellular regions. Thus, transmembrane crosstalk between the galectin lattice and pY14Cav1 promotes FA turnover by stabilizing FAK within FAs defining previously unknown, interdependent roles for galectin-3 and pY14Cav1 in tumor cell migration.
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发表时间: 2007-05-21
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影响因子: --
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