Rab11a通过诱导AQP5脂筏定位调节唾液分泌的机制研究

口腔干燥症主要表现为唾液减少，目前证实只有水通道蛋白5(AQP5)与唾液分泌功能密切相关。M3胆碱能受体活化后，AQP5能快速从涎腺细胞胞内囊泡转移至顶膜并介导水的通透性，是刺激性唾液分泌时水通过腺泡细胞顶膜的主要途径。我们的前期研究证实，刺激状态下AQP5在囊泡膜脂双层的特殊微区域脂筏内的数量增多，并与脂筏一同转位至细胞顶膜。且证实Rab11a与AQP5在涎腺细胞中有共定位，胆碱能受体活化后，能导致富含AQP5囊泡上的Rab11a数量增加，推测Rab11a可能通过诱导AQP5在脂筏内的定位，调节其向细胞顶膜的定向转运。本课题因此拟以人涎腺细胞、正常和口干症大鼠模型为研究对象，探讨Rab11a对AQP5脂筏分布的作用；并研究Rab11a与脂筏的相互作用及其机制；分析它们对AQP5囊泡定向转运以及对唾液液体分泌的影响。为进一步研究涎腺水分泌机理奠定基础，为防治口干症及相关疾病提供新思路。

Xerostomia is mainly manifested in the reduction of saliva. It is verified that only Aquaporin 5 (AQP5) is closely related to the water secreting in salivary glands. After M3 cholinergic receptor being activated, AQP5 is rapidly translocated from the intracellular vesicles to the apical membrane, by which the water permeability is mediated effectively. This process is the main way in that the water crosses the apical membrane of acinar cells when salivary glands are stimulated. Our previous researches confirmed that AQP5 increases in the lipid rafts of specialized vesicle membrane microdomains and AQP5 moves from the cytoplasm to the apical membrane together with lipid rafts in salivary glands, and confirmed that Rab11a can be co-localized with AQP5 in salivary glands and after the cholinergic receptor being activated the amount of Rab11a increases in AQP5 vesicles. We suppose that Rab11a may induce the AQP5’s localization in lipid rafts and may further adjust AQP5’s translocation to the apical membrane of the cells. Therefore, in this study, we will use the Human salivary gland (HSG) cells, the normal and the xerostomia model rats: 1) to discuss the effects of Rab11a on the distribution of AQP5 in lipid raft; 2) to research the interaction between Rab11a and lipid rafts and the corresponding mechanism; 3) finally to clarify the regulating effects of Rab11a and lipid rafts on the transport of AQP5 vesicles and on the corresponding molecular mechanism of water secreting in salivary glands. The fruits of this study are expected to construct bases for the further research on the mechanism of the water secreting in salivary gland and to provide the new trains of thought for the preventive treatment to dry mouth and the associated diseases.