The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion.
The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion.
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DOI：
10.1083/jcb.129.5.1391
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发表时间：
1995-06
影响因子：
7.8
通讯作者：
LILIEN, J
中科院分区：
文献类型：
--
作者：
BALSAMO, J;ERNST, H;ZANIN, MKB;HOFFMAN, S;LILIEN, J
我们之前已经证明，针对鸡神经视网膜N-乙酰半乳糖胺基磷酸转移酶（GalNAcPTase）的单克隆抗体与细胞结合可抑制钙粘蛋白介导的粘附和神经突的生长。我们假设抗体模仿内源性配体的作用。硫酸软骨素蛋白聚糖（CSPGs）是潜在的配体，因为它们抑制粘附和神经突起的生长，并存在于神经元生长的原位屏障中。因此，我们分析了纯化的CSPGs抑制亲同性钙粘蛋白介导的粘附和神经突生长的能力，以及它们直接与GalNAcPTase结合的能力。去除硫酸软骨素链（250-kD PG）后，具有250-kD核心蛋白的蛋白多糖可抑制钙粘蛋白介导的粘附和神经突生长，无论是作为核心蛋白还是作为含有硫酸软骨素的蛋白多糖单体。具有400-kD核心蛋白的蛋白多糖对核心蛋白或单体形式均无抑制作用。用磷脂酰肌醇特异性磷脂酶C处理细胞，去除细胞表面GalNAcPTase，消除这种抑制作用。250-kD核心蛋白与细胞的结合是由抗galnacptase抗体1B11竞争的，这表明1B11和250-kD核心蛋白结合在同一位点或附近。此外，可溶性GalNAcPTase与固定的250-kD核心蛋白结合，而不与固定的400-kD核心蛋白结合。在抑制钙粘蛋白介导的粘附的同时，细胞上250-kD核心蛋白与GalNAcPTase的结合导致β -catenin的酪氨酸磷酸化增强，并使N-cadherin从与细胞骨架的关联中解耦。此外，250-kD PG存在于胚胎鸡视网膜和大脑中，并与GalNAcPTase原位相关。我们得出结论，250-kD PG是GalNAcPTase的内源性配体。250-kD PG与GalNAcPTase结合启动信号级联，涉及β -连环蛋白的酪氨酸磷酸化，改变钙粘蛋白与含肌动蛋白的细胞骨架的关联，从而抑制粘附和神经突的生长。调节GalNacPTase/250-kD PG相互作用对的每个成员的时空表达模式可能会创造相互作用的机会，通过影响钙粘蛋白为基础的形态发生过程来影响发育过程。
We have previously shown that the binding to cells of a monoclonal antibody directed against the chick neural retina N- acetylgalactosaminylphosphotransferase (GalNAcPTase) results in inhibition of cadherin-mediated adhesion and neurite outgrowth. We hypothesized that the antibody mimics the action of an endogenous ligand. Chondroitin sulfate proteoglycans (CSPGs) are potential ligands because they inhibit adhesion and neurite outgrowth and are present in situ at barriers to neuronal growth. We therefore assayed purified CSPGs for their ability to inhibit homophilic cadherin-mediated adhesion and neurite outgrowth, as well as their ability to bind directly to the GalNAcPTase. A proteoglycan with a 250-kD core protein following removal of chondroitin sulfate chains (250-kD PG) inhibits cadherin-mediated adhesion and neurite outgrowth whether presented as the core protein or as a proteoglycan monomer bearing chondroitin sulfate. A proteoglycan with a 400-kD core protein is not inhibitory in either core protein or monomer form. Treatment of cells with phosphatidylinositol-specific phospholipase C, which removes cell surface GalNAcPTase, abolishes this inhibitory effect. Binding of the 250-kD core protein to cells is competed by the anti-GalNAcPTase antibody 1B11, suggesting that 1B11 and the 250-kD core protein bind to the same site or in close proximity. Moreover, soluble GalNAcPTase binds to the immobilized 250-kD core protein but not to the immobilized 400-kD core protein. Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta-catenin and the uncoupling of N-cadherin from its association with the cytoskeleton. Moreover, the 250-kD PG is present in embryonic chick retina and brain and is associated with the GalNAcPTase in situ. We conclude that the 250-kD PG is an endogenous ligand for the GalNAcPTase. Binding of the 250-kD PG to the GalNAcPTase initiates a signal cascade, involving the tyrosine phosphorylation of beta-catenin, which alters the association of cadherin with the actin-containing cytoskeleton and thereby inhibits adhesion and neurite outgrowth. Regulation of the temporal and spatial expression patterns of each member of the GalNacPTase/250-kD PG interactive pair may create opportunities for interaction that influence the course of development through effects on cadherin-based morphogenetic processes.
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DOI：
10.1083/jcb.118.3.671
发表时间：
1992-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Knudsen KA;Wheelock MJ
通讯作者：
Wheelock MJ
影响因子：
4
作者：
BALSAMO, J;PRATT, RS;LILIEN, J
通讯作者：
LILIEN, J
影响因子：
2.8
作者：
GUO, M;DOW, KE;RIOPELLE, RJ
通讯作者：
RIOPELLE, RJ
DOI：
10.1083/jcb.107.6.2329
发表时间：
1988-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Friedlander DR;Hoffman S;Edelman GM
通讯作者：
Edelman GM
影响因子：
11.4
作者：
HAMAGUCHI, M;MATSUYOSHI, N;NAGAI, Y
通讯作者：
NAGAI, Y