RILP对细胞分泌路径的调控作用和分子机制

分泌作用是真核细胞中由囊泡运输介导的一个基本细胞活动。RILP（Rab7 interacting lysosomal protein）是调控内吞作用从晚期内体到溶酶体运输的关键因子，但是其在细胞分泌过程中的作用尚不清楚。我们在前期研究中发现，过表达RILP导致晚期内体/溶酶体高度聚集，同时抑制VSV-G从高尔基体到细胞表面的运输以及Cathepsin D的分泌；进一步研究发现RILP也影响胰岛素分泌小体和黑色素小体的分布、定位。这些结果暗示RILP可能系统性调控细胞分泌过程。本项目拟通过细胞、模式动物等深入探讨RILP对不同分泌路径：调节型分泌(regulatory secretion，如胰岛素分泌）和组成型分泌(constitutive secretion，如黑色素分泌)的调控作用；寻找新的RILP相互作用因子，明确RILP在不同分泌路径中的调控网络，揭示RILP调控细胞分泌的分子机制。

Secretion is a foundmental event in eukayotic cells which is mediated by membrane trafficking machineries. RILP (Rab7 interacting lysosomal protein) is the key regulator in late endosomal/lysosomal trafficking, however, the role of RILP in secretion is not clear yet. Our primary investigations demonstrated that over-expression of RILP induces clustering of the late endosomes/lysosomes and inhibits the transport of VSV-G protein from Glogi to plasma membrane, and the secretion of Cathepsin D; Further investigations indicated that RILP regulates the distribution and location of insulin secretory granule and melanosome. These results suggest that RILP may systematically participate in regulating secretory pathway. In this project, we will continue to investigate the roles of RILP in regulatory secretion pathway (such as secretion of insulin) and constitutive secretion pathway (such as melanin pigmentation) using cell model or animal model; In addition, we will search for novel interacting partners for RILP to define the interaction network in regulating secretion pathway, establishing novel mechanisms for RILP regulating cell secretion pathway.