Kelm S, Pelz A, Schauer R, Filbin M T, Tang S, de Bellard M E, Schnaar R L, Mahoney J A, Hartnell A, Bradfield P
Biochemisches Institut II, University of Kiel, Germany.
Curr Biol. 1994 Nov 1;4(11):965-72. doi: 10.1016/s0960-9822(00)00220-7.
Protein-carbohydrate interactions are believed to be important in many biological processes that involve cell-cell communication. Apart from the selectins, the only well-characterized vertebrate sialic acid-dependent adhesion molecules are CD22 and sialoadhesin; CD22 is a member of the immunoglobulin superfamily that is expressed by B lymphocytes and sialoadhesin is a macrophage receptor. The recent cloning of the gene encoding sialoadhesin has shown that it is also immunoglobulin-like. Both proteins share sequence similarity with the myelin-associated glycoprotein, an adhesion molecule of oligodendrocytes and Schwann cells that has been implicated in the process of myelination, raising the important question of whether myelin-associated glycoprotein is also a sialic acid-binding protein.
We have investigated the binding properties of these three receptors when expressed either in monkey COS cells or as chimaeric proteins containing the Fc portion of human immunoglobulin G. We demonstrate that, like sialoadhesin and CD22, myelin-associated glycoprotein mediates cell adhesion by binding to cell-surface glycans that contain sialic acid. We have dissected the specificities of these three adhesins further: whereas sialoadhesin binds equally to the sugar moieties NeuAc alpha 2-->3Gal beta 1-->3(4)GlcNAc or NeuAc alpha 2-->3Gal beta 1-->3GalNAc, myelin-associated glycoprotein recognizes only NeuAc alpha 2-->3Gal beta 1-->3GalNAc and CD22 binds specifically to NeuAc alpha 2-->6Gal beta 1-->4GlcNAc. Furthermore, we show that the recognition of sialylated glycans on the surfaces of particular cell types leads to the selective binding of sialoadhesin to neutrophils, myelin-associated glycoprotein to neurons and CD22 to lymphocytes.
Our findings demonstrate that a subgroup of the immunoglobulin superfamily can mediate diverse biological processes through recognition of specific sialylated glycans on cell surfaces. We propose that this subgroup of proteins be called the sialoadhesin family.
蛋白质 - 碳水化合物相互作用在许多涉及细胞间通讯的生物学过程中被认为是重要的。除了选择素外，唯一特征明确的脊椎动物唾液酸依赖性粘附分子是CD22和唾液酸粘附素；CD22是免疫球蛋白超家族的成员，由B淋巴细胞表达，而唾液酸粘附素是一种巨噬细胞受体。最近编码唾液酸粘附素的基因克隆表明它也是免疫球蛋白样的。这两种蛋白质与髓鞘相关糖蛋白具有序列相似性，髓鞘相关糖蛋白是少突胶质细胞和施万细胞的一种粘附分子，与髓鞘形成过程有关，这就提出了一个重要问题，即髓鞘相关糖蛋白是否也是一种唾液酸结合蛋白。
我们研究了这三种受体在猴COS细胞中表达时或作为含有人类免疫球蛋白G的Fc部分的嵌合蛋白时的结合特性。我们证明，与唾液酸粘附素和CD22一样，髓鞘相关糖蛋白通过与含有唾液酸的细胞表面聚糖结合来介导细胞粘附。我们进一步剖析了这三种粘附素的特异性：唾液酸粘附素与糖部分NeuAcα2→3Galβ1→3(4)GlcNAc或NeuAcα2→3Galβ1→3GalNAc同等结合，而髓鞘相关糖蛋白仅识别NeuAcα2→3Galβ1→3GalNAc，CD22则特异性结合NeuAcα2→6Galβ1→4GlcNAc。此外，我们表明，对特定细胞类型表面唾液酸化聚糖的识别导致唾液酸粘附素选择性结合中性粒细胞，髓鞘相关糖蛋白结合神经元，CD22结合淋巴细胞。
我们的研究结果表明，免疫球蛋白超家族的一个亚组可以通过识别细胞表面特定的唾液酸化聚糖来介导多种生物学过程。我们建议将这一蛋白质亚组称为唾液酸粘附素家族。
