膜的融合是基本生命活动所必须的。进化上保守的ATP酶NSF是介导细胞内膜融合的关键蛋白，在膜融合核心驱动复合物SNARE去组装过程发挥决定作用。目前对NSF介导的SNARE去组装机制已经有了较深了解，但对NSF自身的调控机制还知之甚少。我们最近发现了一个全新的NSF结合蛋白Mon1b。初步研究结果显示Mon1b是重要的NSF调控蛋白，参与早期内吞体（early endosome）的融合过程。进一步研究发现Mon1b能够激活NSF的ATP酶活性。本项目将从以下几方面深入研究Mon1b和NSF协同调控早期内吞体膜融合的分子细胞机理：1）揭示Mon1b对NSF的功能调控及分子机制；2）阐明Mon1b 对NSF的调节是否/如何影响SNARE复合物组装和去组装；3）确定Mon1b和NSF在早期内吞体膜融合过程中的协同功能。本项目研究结果将为理解NSF-SNARE复合体介导的膜融合过程提供重要机制。

Membrane fusion is one of the most fundamental processes in life. The evolutionally conserved ATPase, NSF (N-ethylmaleimide-sensitive fusion protein), is a critical determinant for SNARE disassembly during membrane fusion process. Although the mechanisms underlying NSF driven SNARE disassembly have been extensively studied, how NSF is regulated during the process remains largely unknown. Most recently, we characterized Mon1b as a novel NSF-binding protein. Our preliminary data suggest that Mon1b is a critical regulator of NSF and plays crucial functions for early endosome fusion. More importantly, Mon1b could stimulate the ATPase activity of NSF in vitro. In this project, we focus on the following experiments to address the molecular and cellular mechanisms by which Mon1b acts as an adaptor of NSF to control the early endosome fusion: 1) Explore the molecular mechanism by which Mon1b regulates NSF; 2) Determine whether and how Mon1b-NSF interaction contributes to SNARE assembly and disassembly; 3) Investigate the functional significance of Mon1b in NSF controlled early endosome fusion. Our future research results will provide novel mechanism to fully understand the NSF-SNARE driven membrane fusion.