Center for Oral Health and Systemic Disease, School of Dentistry, 501 South Preston Street, Room 331, University of Louisville, Louisville, KY 40202, USA.
J Dent Res. 2011 Sep;90(9):1085-90. doi: 10.1177/0022034511410699. Epub 2011 May 31.
Molecular interactions that direct trafficking of secreted proteins are not well-described in salivary glands. Here, we report that the soluble cargo protein Parotid Secretory Protein (PSP) is bound to the membranes of secretory granules isolated from rat parotids. This is apparently due to specific interaction with phosphatidylinositol phosphates (PtdInsP). PSP binds PtdIns(3,4)P(2), 10-fold greater than PtdIns(3,5)P(2) or PtdIns(4)P, and does not bind PtdIns(3)P or PtdIns(5)P. Human PSP synthesized in vitro also binds PtdIns(3,4)P(2). Bacterially expressed rat PSP binds PtdIns(3,4)P(2) with a K(d) of 2.4 x 10(-11) M. Other major secretory proteins (amylase, proline-rich protein) are not bound to isolated granule membranes and do not bind phosphatidylinositol phosphates. Immunofluorescence shows PtdIns(3,4)P(2) at the secretory granules, and fluorescent PtdIns(3,4)P(2) can flip from the outer leaflet to the inner leaflet of the membrane. Binding of PSP to PtdInsPs may contribute to sorting during the formation of the secretory granules, or sorting by retention during maturation of the granules.
在唾液腺中，指导分泌蛋白运输的分子相互作用尚未得到很好的描述。在这里，我们报告说，可溶性货物蛋白腮腺分泌蛋白（PSP）与从大鼠腮腺中分离的分泌颗粒的膜结合。这显然是由于与磷酸肌醇磷酸（PtdInsP）的特异性相互作用。PSP 结合 PtdIns(3,4)P(2)的能力比 PtdIns(3,5)P(2)或 PtdIns(4)P 高 10 倍，并且不结合 PtdIns(3)P 或 PtdIns(5)P。体外合成的人 PSP 也结合 PtdIns(3,4)P(2)。在细菌中表达的大鼠 PSP 与 PtdIns(3,4)P(2)的结合 K(d)为 2.4 x 10(-11) M。其他主要分泌蛋白（淀粉酶、富含脯氨酸的蛋白）不与分离的颗粒膜结合，也不与磷酸肌醇磷酸结合。免疫荧光显示 PtdIns(3,4)P(2)在分泌颗粒上，荧光 PtdIns(3,4)P(2)可以从膜的外叶翻转到内叶。PSP 与 PtdInsPs 的结合可能有助于在分泌颗粒形成过程中的分拣，或者在颗粒成熟过程中通过保留来分拣。
