管腔发育是肾小管发生的关键阶段,尽管其分子机制在很大程度上是未知的。在这项研究中,我们发现了一个含有ELMO结构域的3(ELMOD3),属于ADP核糖基化因子GTP酶激活蛋白家族,是形成Ciona幼虫的脊索腔所必需的。我们证明ELMOD3与脂筏蛋白Flotillin2相互作用并调节其亚细胞定位。Flotillin2的功能丧失阻止了脊索腔的形成。此外,我们发现ELMOD3也与Rab1A相互作用,它是用于囊泡运输的调节GTP酶,位于脊索细胞表面。Rab1A突变阻止了管腔形成,表现ELMOD3和Flotillin2的功能丧失。我们的发现进一步表明Rab1A相互作用影响了Flotillin2的定位。因此,我们确定了ELMOD3与Rab1A相互作用的独特途径,控制了Flotillin2介导的囊泡从细胞质到顶膜的运输,Ciona脊索腔形成所需。
Lumen development is a crucial phase in tubulogenesis, although its molecular mechanisms are largely unknown. In this study, we discovered an ELMO domain-containing 3 (
ELMOD3), which belongs to ADP-ribosylation factor GTPase-activating protein family, was necessary to form the notochord lumen in Ciona larvae. We demonstrated that
ELMOD3 interacted with lipid raft protein Flotillin2 and regulated its subcellular localization. The loss-of-function of Flotillin2 prevented notochord lumen formation. Furthermore, we found that
ELMOD3 also interacted with Rab1A, which is the regulatory GTPase for vesicle trafficking and located at the notochord cell surface. Rab1A mutations arrested the lumen formation, phenocopying the loss-of-function of
ELMOD3 and Flotillin2. Our findings further suggested that Rab1A interactions influenced Flotillin2 localization. We thus identified a unique pathway in which
ELMOD3 interacted with Rab1A, which controlled the Flotillin2-mediated vesicle trafficking from cytoplasm to apical membrane, required for Ciona notochord lumen formation.