Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment.
Plasmin-sensitive dibasic sequences in the third fibronectin-like domain of L1-cell adhesion molecule (CAM) facilitate homomultimerization and concomitant integrin recruitment.
复制标题
DOI：
10.1083/jcb.149.7.1485
复制
发表时间：
2000-06-26
期刊：
影响因子：
--
通讯作者：
Montgomery AM
中科院分区：
文献类型：
--
作者：
Silletti S;Mei F;Sheppard D;Montgomery AM
L1是神经组织发生所必需的多结构域跨膜神经识别分子。虽然L1的免疫球蛋白样结构域中的部分涉及嗜异性和嗜同性结合，但纤连蛋白（FN）样重复序列的功能在很大程度上仍未得到解决。在这里，我们证明了第三FN样重复的L1（FN 3）自发homomultimerizes形成三聚体和更高阶的复合物。值得注意的是，这些复合物支持与几种整联蛋白（包括αvβ3和α5β1）的直接RGD非依赖性相互作用。衍生自FN 3（GSQRKHSKRHIHKDHV 852）的假定C-C′环的肽也形成三聚体复合物，并支持αvβ3和α5β1结合。该肽或FN 3结构域内的二元RK 841和KR 845序列的取代限制了多聚化并消除了整联蛋白结合。有证据表明，FN 3结构域的多聚化和整联蛋白与FN 3结构域的结合受到其他结构域施加的构象限制和纤溶酶介导的序列RK↓HSK↓ RH 846内的切割的调节。整合素α9β1也识别FN 3结构域，以限制于细胞-细胞接触位点的方式与L1共定位。我们提出，远端受体连接事件在细胞-细胞界面可能会诱导构象变化内的L1胞外域，最终在受体多聚化和整合素招聘通过与FN 3结构域的相互作用。
L1 is a multidomain transmembrane neural recognition molecule essential for neurohistogenesis. While moieties in the immunoglobulin-like domains of L1 have been implicated in both heterophilic and homophilic binding, the function of the fibronectin (FN)-like repeats remains largely unresolved. Here, we demonstrate that the third FN-like repeat of L1 (FN3) spontaneously homomultimerizes to form trimeric and higher order complexes. Remarkably, these complexes support direct RGD-independent interactions with several integrins, including αvβ3 and α5β1. A pep- tide derived from the putative C-C′ loop of FN3 (GSQRKHSKRHIHKDHV852) also forms trimeric complexes and supports αvβ3 and α5β1 binding. Substitution of the dibasic RK841 and KR845 sequences within this peptide or the FN3 domain limited multimerization and abrogated integrin binding. Evidence is presented that the multimerization of, and integrin binding to, the FN3 domain is regulated both by conformational constraints imposed by other domains and by plasmin- mediated cleavage within the sequence RK↓HSK↓RH846. The integrin α9β1, which also recognizes the FN3 domain, colocalizes with L1 in a manner restricted to sites of cell–cell contact. We propose that distal receptor ligation events at the cell–cell interface may induce a conformational change within the L1 ectodomain that culminates in receptor multimerization and integrin recruitment via interaction with the FN3 domain.
登录
查看更多内容
DOI：
10.1083/jcb.130.3.733
发表时间：
1995-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Burgoon MP;Hazan RB;Phillips GR;Crossin KL;Edelman GM;Cunningham BA
通讯作者：
Cunningham BA
影响因子：
5.4
作者：
Ebeling, O;Duczmal, A;Altevogt, P
通讯作者：
Altevogt, P
影响因子：
16.2
作者：
IGNELZI, MA;MILLER, DR;MANESS, PF
通讯作者：
MANESS, PF
影响因子：
3.5
作者：
Jung, M;Petrausch, B;Stuermer, CAO
通讯作者：
Stuermer, CAO
DOI：
10.1002/neu.480280304
发表时间：
1995-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
APPEL, F;HOLM, J;SCHACHNER, M
通讯作者：
SCHACHNER, M