溶酶体相关细胞器(LROs)是一大类与溶酶体类似，但形态和功能却不尽相同的细胞器。线虫的LROs是肠道颗粒。本研究通过突变体筛选和基因克隆，得到了一个新的控制肠细胞LROs 生成和动态平衡的基因lmd-2。在lmd-2(yq114)突变体中，LROs体积异常增大，并且呈现为GLO-1阳性。进一步研究发现，lmd-2突变体中肠细胞LROs增大的表型依赖于GLO-1及其GEF(GLO-3/CCZ-1/GLO-4)。蛋白质互作研究表明LMD-2可直接与活性形式的GLO-1(Q71L)相互作用。GLO-1是小G蛋白Rab家族成员，其哺乳动物同源蛋白为Rab32/Rab38,目前LMD-2在人类中的同源物LYSMD1的功能还不得而知。因此本项目将重点研究1.以秀丽隐杆线虫为模式生物阐明LMD-2对LROs的调控机制；2.以小鼠为模型探究LYSMD1蛋白对哺乳动物LROs的调控机制。

Lysosome-related organelles (LROs) are a type of organelles with diverse morphologies and functions.The functions and regulatory mechanisms of LROs are complex and remain to be elucidated.In C.elegans,gut granules are generally regarded as LROs.Using forward genetic tools,we cloned a gene,lmd-2,which is important for the biogenesis LROs in the intestine. lmd-2 mutants yq114 contain enlarged LROs that are positive for GLO-1,a Rab32/38 homolog.Loss of GLO-1 and its guanine exchange factors(GEF) GLO-3,GLO-4 and CCZ-1 suppresses the LRO phenotype in lmd-2 mutants.The human homolog of LMD-2,LYSMD1,was not characterized before. In vitro,LMD-2 interacts with the constitutively active form of GLO-1,GLO-1(Q71L). Future study will be focused on the mechanism of how LMD-2 regulate LROs size through GLO-1 then open the door for understanding the function of human protein LYSMD1.