Members of the Tre2-Bub2-Cdc16 (TBC) family often function to regulate membrane trafficking and to control signaling transductions pathways. As a member of the TBC family, TBC1D23 is critical for endosome-to-Golgi cargo trafficking by serving as a bridge between Golgi-bound golgin-97/245 and the WASH/FAM21 complex on endosomal vesicles. However, the exact mechanisms by which TBC1D23 regulates cargo transport are poorly understood. Here, we present the crystal structure of the N-terminus of TBC1D23 (D23^N), which consists of both the TBC and rhodanese domains. We show that the rhodanese domain is unlikely to be an active sulfurtransferase or phosphatase, despite containing a putative catalytic site. Instead, it packs against the TBC domain and forms part of the platform to interact with golgin-97/245. Using the zebrafish model, we show that impacting golgin-97/245-binding, but not the putative catalytic site, impairs neuronal growth and brain development. Altogether, our studies provide structural and functional insights into an essential protein that is required for organelle-specific trafficking and brain development.

Tre2-Bub2-Cdc16（TBC）家族的成员通常起到调节膜运输和控制信号转导途径的作用。作为TBC家族的成员，TBC1D23通过在高尔基体结合的golgin-97 / 245和内体小泡上的WASH / FAM21复合体之间架起桥梁，对于从内体到高尔基体的货物运输至关重要。但是，TBC1D23调节货物运输的确切机制了解甚少。在这里，我们介绍了TBC1D23（D23 ^N），它由TBC和罗丹语域组成。我们显示，尽管含有推定的催化位点，但若丹群岛域不太可能是活性硫转移酶或磷酸酶。取而代之的是，它与TBC域相对应，并构成与golgin-97 / 245交互的平台的一部分。使用斑马鱼模型，我们表明影响golgin 97/245绑定，但不是推定的催化位点，损害神经元生长和大脑发育。总而言之，我们的研究提供了对细胞器特异性运输和大脑发育所需的必需蛋白质的结构和功能方面的见解。