From the Institutes of Biomedicine.
J Biol Chem. 2014 Mar 21;289(12):8375-89. doi: 10.1074/jbc.M114.552133. Epub 2014 Feb 7.
Hyaluronan synthases (HAS1-3) are unique in that they are active only when located in the plasma membrane, where they extrude the growing hyaluronan (HA) directly into cell surface and extracellular space. Therefore, traffic of HAS to/from the plasma membrane is crucial for the synthesis of HA. In this study, we have identified Rab10 GTPase as the first protein known to be involved in the control of this traffic. Rab10 colocalized with HAS3 in intracellular vesicular structures and was co-immunoprecipitated with HAS3 from isolated endosomal vesicles. Rab10 silencing increased the plasma membrane residence of HAS3, resulting in a significant increase of HA secretion and an enlarged cell surface HA coat, whereas Rab10 overexpression suppressed HA synthesis. Rab10 silencing blocked the retrograde traffic of HAS3 from the plasma membrane to early endosomes. The cell surface HA coat impaired cell adhesion to type I collagen, as indicated by recovery of adhesion following hyaluronidase treatment. The data indicate a novel function for Rab10 in reducing cell surface HAS3, suppressing HA synthesis, and facilitating cell adhesion to type I collagen. These are processes important in tissue injury, inflammation, and malignant growth.
透明质酸合酶（HAS1-3）的独特之处在于，它们只有在位于质膜中时才具有活性，在质膜中，它们将不断生长的透明质酸（HA）直接挤出到细胞表面和细胞外空间。因此，HAS 向/从质膜的运输对于 HA 的合成至关重要。在这项研究中，我们已经确定 Rab10 GTPase 是第一个已知参与控制这种运输的蛋白质。Rab10 与 HAS3 在细胞内囊泡结构中共定位，并与从分离的内体小泡中免疫沉淀的 HAS3 共沉淀。Rab10 的沉默增加了 HAS3 的质膜驻留，导致 HA 分泌显著增加和细胞表面 HA 涂层增大，而 Rab10 的过表达抑制了 HA 的合成。Rab10 的沉默阻断了 HAS3 从质膜向早期内体的逆行运输。细胞表面的 HA 涂层会损害细胞与 I 型胶原的黏附性，如用透明质酸酶处理后黏附性恢复所表明的那样。数据表明 Rab10 在减少细胞表面 HAS3、抑制 HA 合成以及促进细胞与 I 型胶原黏附方面具有新的功能。这些过程在组织损伤、炎症和恶性生长中很重要。
