Fibronectin and heparin binding domains of latent TGF-β binding protein (LTBP)-4 mediate matrix targeting and cell adhesion
Fibronectin and heparin binding domains of latent TGF-β binding protein (LTBP)-4 mediate matrix targeting and cell adhesion
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DOI：
10.1016/j.yexcr.2008.05.010
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Koli, Katri
中科院分区：
文献类型：
--
作者：
Kantola, Anna K.;Keski-Oja, Jorma;Koli, Katri
潜伏转化生长因子（TGF）-β结合蛋白是参与调节TGF-β螯合和活化的细胞外基质（ECM）蛋白。在这项研究中，我们已经确定了LTBP-4的结合域，介导基质靶向和细胞粘附。发现LTBP-4具有肝素结合活性，尤其是在其N-末端区域。LTBP-4的C-末端结构域支持成纤维细胞粘附，这是一种被可溶性肝素降低的性质。此外，我们发现LTBP-4直接与纤连蛋白（FN）结合，这是LTBP-4的基质组装所必需的。FN结合位点也位于N端区域。有趣的是，肝素能够减少LTBP-4与FN的结合。在成纤维细胞培养物中，LTBP-4首先与FN共定位，随后与FN-1共定位，这表明FN在LTBP-4的早期组装中起作用。在FN-/-成纤维细胞中，LTBP介导的ECM靶向受到干扰，导致TGF-β活性增加。这些结果揭示了新的分子相互作用，这对ECM靶向明显重要，但也是LTBP-4作为粘附分子的新功能的证据。(c)2008年爱思唯尔公司All rights reserved.
Latent transforming growth factor (TGF)-beta binding proteins are extracellular matrix (ECM) proteins involved in the regulation of TGF-beta sequestration and activation. In this study, we have identified binding domains in LTBP-4, which mediate matrix targeting and cell adhesion. LTBP-4 was found to possess heparin binding activity, especially in its N-terminal region. The C-terminal domain of LTBP-4 supported fibroblast adhesion, a property reduced by soluble heparin. In addition, we found that LTBP-4 binds directly to fibronectin (FN), which was indispensable for the matrix assembly of LTBP-4. The FN binding sites were also located in the N-terminal region. Interestingly, heparin was able to reduce the binding of LTBP-4 to FN. In fibroblast cultures, LTBP-4 colocalized first with FN and subsequently with fibrillin-1, pointing to a role for FN in the early assembly of LTBP-4. In FN-/- fibroblasts, LTBP-mediated ECM targeting was disturbed, resulting in increased TGF-beta activity. These results revealed new molecular interactions which are evidently important for the ECM targeting, but which also are evidence of novel functions for LTBP-4 as an adhesion molecule. (c) 2008 Elsevier Inc. All rights reserved.