Rab11在果蠅神經元樹突修剪所扮演之角色

Abstract

在脊椎動物和無脊椎動物的發育時期都被發現有神經重塑的過程，神經會接收外源及內源的刺激後引起重塑過程，將神經網路完善化並使其成為在成熟動物中可正常運作的迴路。樹突修剪是神經重塑的其中一種，並會發生在果蠅變態過程中的感覺神經元。果蠅感覺神經元的樹突修剪需要Ik2激酶和其下游的調控因子Spn-F。在此篇研究中，已知在胞吐和再循環過程中扮演重要角色的小GTP酶Rab11被發現作為樹突修剪和樹突型態發生重要的調控因子。此外，我們也藉由基因實驗和蛋白質成像實驗發現Rab11在樹突修剪中可能有需要倚靠Spn-F的功能及不須倚靠Spn-F的功能，其中Rab11不須倚靠Spn-F的功能是參與在負向調控細胞膜上的其中一種細胞黏附分子，Nrg。最後，我們也發現三個已知的Rab11鳥嘌呤核苷酸轉換因子有參與在調控樹突型態發生。總結來說，此篇研究指出了Rab11在神經網路的建立及重塑皆扮演著不可或缺的角色。

During development, neuronal remodeling refines neuronal networks in response to external and internal stimuli to establish fully functioning wiring in both vertebrates and invertebrates. Dendrite pruning, which is one of the remodeling processes, occurs in Drosophila sensory neurons during metamorphosis and this pruning process requires Ik2 kinase and its downstream regulator, Spindle-F (Spn-F). Here we demonstrate that a small GTPase Rab11, a regulator in exocytic and recycling pathway, is essential for both dendrite pruning and dendrite morphogenesis. Moreover, our genetic studies and protein imaging experiments revealed that Rab11 could have a Spn-F-dependent function and a Spn-F-independent function, which involves in the degradation of a cell-adhesion molecule Neuroglian (Nrg), in dendrite pruning. Also, we identified three Rab11 guanine nucleotide exchange factors (GEFs) as regulators for dendrite morphogenesis. Altogether, we point out the importance of Rab11 in both establishment and refinement of neuronal networks.