Syndecans are single-pass transmembrane proteins on the cell surface that are involved in various cellular functions. Previously, we reported that both homo- and hetero-form of syndecan dimers affected their functionality. However, little is known about the structural role of the transmembrane domain of syndecan-3. A series of glutathione-S-transferase syndecan-3 proteins showed that syndecan-3 formed SDS-resistant dimers and oligomers. SDS-resistant oligomer formation was barely observed in the syndecan deletion mutants lacking the transmembrane domain. Interestingly, the presence of an alanine 397 residue in the transmembrane domain correlated with SDS-resistant oligomer, and its replacement by phenylalanine (AF mutant) significantly reduced SDS-resistant oligomer formation. Beside the AF mutant significantly reduced syndecan-3 mediated cellular processes such as cell adhesion, migration and neurite outgrowth of SH-SY5Y neuroblastoma. Furthermore, the alanine residue regulated hetero-oligomer formation of syndecan-3, and hetero-oligomer formation significantly reduced syndecan-3-mediated neurite outgrowth of SH-SY5Y cells. Taken together, all these data suggest that syndecan-3 has a specific feature of oligomerization by the transmembrane domain and this oligomerization tendency is crucial for the function of syndecan-3.

中文翻译：

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跨膜结构域中丙氨酸397残基介导的寡聚化对sydecan-3功能至关重要。

Syndecans是细胞表面上涉及多种细胞功能的单程跨膜蛋白。先前，我们报道了同型双聚体的同型和异型均影响其功能。但是，关于syndecan-3跨膜结构域的结构作用知之甚少。一系列谷胱甘肽-S-转移酶syndecan-3蛋白表明，syndecan-3形成了抗SDS的二聚体和寡聚体。在缺乏跨膜结构域的syndecan缺失突变体中几乎未观察到SDS抗性低聚物的形成。有趣的是，跨膜结构域中丙氨酸397残基的存在与SDS抗性低聚物相关，其被苯丙氨酸（AF突变体）替代显着减少了SDS抗性低聚物的形成。除了AF突变体，SH-SY5Y神经母细胞瘤还可以显着减少syndecan-3介导的细胞过程，例如细胞粘附，迁移和神经突生长。此外，丙氨酸残基调节了syndecan-3的杂合寡聚体的形成，而杂合寡聚体的形成显着减少了SH-SY5Y细胞的syndecan-3介导的神经突向外生长。综上所述，所有这些数据表明，syndecan-3具有跨膜结构域寡聚化的特定特征，这种低聚趋势对于syndecan-3的功能至关重要。