Glycosylation of CD44 negatively regulates its recognition of hyaluronan.
Glycosylation of CD44 negatively regulates its recognition of hyaluronan.
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DOI：
10.1084/jem.182.2.419
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发表时间：
1995-08-01
期刊：
影响因子：
--
通讯作者：
Kincade PW
中科院分区：
文献类型：
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作者：
Katoh S;Zheng Z;Oritani K;Shimozato T;Kincade PW
虽然CD 44在多种细胞类型上表达，但很少有人使用它来识别配体透明质酸（HA）。中国仓鼠卵巢细胞的糖基化缺陷克隆（Lec 8）结合HA，证明不需要添加完整的唾液酸补体来完全加工糖蛋白。相反，随后的研究结果表明，CD 44上的复合糖实际上可以抑制配体识别。两个亚克隆的野生型中国仓鼠卵巢细胞表面的CD 44相似的金额的基础上分离的HA结合，并发现不同的CD 44的大小，以及与荧光凝集素染色。用衣霉素处理非结合克隆减小了蛋白质的大小，并允许细胞通过CD 44识别HA。该功能也可通过去糖基化酶（内切糖苷酶F和N-糖苷酶F的混合物或单独的神经氨酸酶）处理诱导。然后，用一系列正常和转化的鼠细胞寻找糖基化在调节粘附中的可能作用。糖基化的破坏或去糖基化酶的治疗没有诱导白细胞介素7依赖性前B细胞系中的配体结合，并且脾B细胞似乎也处于非活性状态。一些正常的B细胞在用脂多糖或白细胞介素5刺激后获得识别HA的能力，并且具有独特的表面特征（免疫球蛋白D的丢失和CD 43的获得）。另外一个活化细胞亚群可能处于过渡状态，因为神经氨酸酶处理后细胞与配体结合。神经氨酸酶处理后，纯化的CD 44-免疫球蛋白融合蛋白的配体结合能力显著增加。因此，该分子的差异糖基化足以影响其识别功能。涉及HA的细胞粘附可以通过多种机制调节，其中之一涉及CD 44的可变糖基化。
Although CD44 is expressed on a wide variety of cell types, few of them use it to recognize the ligand hyaluronan (HA). A glycosylation- defective clone of Chinese hamster ovary cells (Lec 8) bound HA, demonstrating that complete processing of glycoproteins with addition of a full complement of sialic acid is not required. On the contrary, subsequent findings revealed that complex sugars on CD44 can actually inhibit ligand recognition. Two subclones of wild-type Chinese hamster ovary cells with similar amounts of surface CD44 were isolated on the basis of HA binding and found to differ with respect to CD44 size as well as staining with fluorescent lectins. Treatment of the nonbinding clone with tunicamycin reduced the size of the protein and allowed the cells to recognize HA via CD44. This function was also induced by treatment with deglycosylating enzymes (either a mixture of endoglycosidase F and N-glycosidase F or neuraminidase alone). A possible role for glycosylation in regulation of adhesion was then sought with a series of normal and transformed murine cells. Disruption of glycosylation or treatment with deglycosylating enzymes did not induce ligand binding in an interleukin 7-dependent pre-B cell line, and splenic B cells also appeared to be in an inactive state. Some normal B cells acquired the ability to recognize HA after stimulation with lipopolysaccharide or interleukin 5 and had distinctive surface characteristics (loss of immunoglobulin D and acquisition of CD43). An additional subset of activated cells might have been in a transitional state, because the cells bound ligand after neuraminidase treatment. The ligand-binding ability of a purified CD44-immunoglobulin fusion protein dramatically increased after neuraminidase treatment. Thus, differential glycosylation of this molecule is sufficient to influence its recognition function. Cell adhesion involving HA can be regulated by multiple mechanisms, one of which involves variable glycosylation of CD44.