A cryptic fragment from fibronectin's III1 module localizes to lipid rafts and stimulates cell growth and contractility.
A cryptic fragment from fibronectin's III1 module localizes to lipid rafts and stimulates cell growth and contractility.
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DOI：
10.1083/jcb.200112031
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发表时间：
2002-07-08
期刊：
影响因子：
--
通讯作者：
Kowalski K
中科院分区：
文献类型：
--
作者：
Hocking DC;Kowalski K
细胞与细胞外基质（ECM）形式的纤连蛋白（FN）的相互作用触发了生长、迁移和细胞骨架组织的变化，这些变化与可溶性FN产生的变化不同。随着细胞存款和重塑其FN基质，暴露的新的表位可能会引发独特的反应，基质FN。为了确定FN的III 1模块内的基质裂解位点是否调节细胞生长或细胞骨架组织，通过将III 1（III 1H）的隐蔽的肝素结合COOH末端片段直接连接到整合素结合III 8 -10模块（谷胱甘肽-S-转移酶[GST]-III 1H，8-10）来构建具有基质FN性质的重组FN。GST-III 1H，8-10特异性刺激细胞生长和收缩性的增加;单独的整联蛋白连接是无效的。缺乏整合素结合结构域的构建体（GST-Ⅲ 1H，2-4）保留了刺激细胞收缩的能力，但不能刺激细胞生长。GST-Ⅲ 1H，2-4和基质FN与小窝蛋白共定位，并通过需要硫酸乙酰肝素蛋白聚糖的机制与低密度膜复合物分离。破坏小窝抑制FN和III 1H介导的细胞收缩和生长的增加。这些数据表明，ECM FN的一部分分区成脂筏和差异调节细胞骨架的组织和生长，在一定程度上，通过暴露的构象不稳定的III 1模块内的新表位。
The interaction of cells with the extracellular matrix (ECM) form of fibronectin (FN) triggers changes in growth, migration, and cytoskeletal organization that differ from those generated by soluble FN. As cells deposit and remodel their FN matrix, the exposure of new epitopes may serve to initiate responses unique to matrix FN. To determine whether a matricryptic site within the III1 module of FN modulates cell growth or cytoskeletal organization, a recombinant FN with properties of matrix FN was constructed by directly linking the cryptic, heparin-binding COOH-terminal fragment of III1 (III1H) to the integrin-binding III8–10 modules (glutathione-S-transferase [GST]–III1H,8–10). GST–III1H,8–10 specifically stimulated increases in cell growth and contractility; integrin ligation alone was ineffective. A construct lacking the integrin-binding domain (GST–III1H,2–4) retained the ability to stimulate cell contraction, but was unable to stimulate cell growth. Both GST–III1H,2–4 and matrix FN colocalized with caveolin and fractionated with low-density membrane complexes by a mechanism that required heparan sulfate proteoglycans. Disruption of caveolae inhibited the FN- and III1H-mediated increases in cell contraction and growth. These data suggest that a portion of ECM FN partitions into lipid rafts and differentially regulates cytoskeletal organization and growth, in part, through the exposure of a neoepitope within the conformationally labile III1 module.
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影响因子：
15.9
作者：
Woods, A
通讯作者：
Woods, A
DOI：
10.1083/jcb.140.6.1357
发表时间：
1998-03-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Keller P;Simons K
通讯作者：
Simons K
影响因子：
4.1
作者：
INGHAM, KC;BREW, SA;ATHA, DH
通讯作者：
ATHA, DH
影响因子：
4.8
作者：
Sechler, JL;Schwarzbauer, JE
通讯作者：
Schwarzbauer, JE
DOI：
10.1016/0167-4838(92)90234-5
发表时间：
1992-02-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LITVINOVICH, SV;NOVOKHATNY, VV;INGHAM, KC
通讯作者：
INGHAM, KC