Table_1_Monensin Sensitive 1 Regulates Dendritic Arborization in Drosophila by Modulating Endocytic Flux.XLSX

Monensin Sensitive 1 (Mon1) is a component of the Mon1:Ccz1 complex that mediates Rab5 to Rab7 conversion in eukaryotic cells by serving as a guanine nucleotide exchange factor for Rab7 during vesicular trafficking. We find that Mon1 activity modulates the complexity of Class IV dendritic arborization (da) neurons during larval development. Loss of Mon1 function leads to an increase in arborization and complexity, while increased expression, leads to reduced arborization. The ability of Mon1 to influence dendritic development is possibly a function of its interactions with Rab family GTPases that are central players in vesicular trafficking. Earlier, these GTPases, specifically Rab1, Rab5, Rab10, and Rab11 have been shown to regulate dendritic arborization. We have conducted genetic epistasis experiments, by modulating the activity of Rab5, Rab7, and Rab11 in da neurons, in Mon1 mutants, and demonstrate that the ability of Mon1 to regulate arborization is possibly due to its effect on the recycling pathway. Dendritic branching is critical for proper connectivity and physiological function of the neuron. An understanding of regulatory elements, such as Mon1, as demonstrated in our study, is essential to understand neuronal function.

Monensin Sensitive 1 (Mon1) 是Mon1:Ccz1复合物的组分之一，该复合物在真核细胞的囊泡运输过程中，作为Rab7的鸟苷酸交换因子（guanine nucleotide exchange factor），介导Rab5向Rab7的转化。本研究发现，Mon1的活性可调控幼虫发育阶段IV型树突分支（dendritic arborization，da）神经元的分支复杂度。Mon1功能缺失可导致树突分支增多、复杂度提升，而Mon1表达上调则会抑制树突分支的形成。Mon1影响神经元树突发育的能力，可能与其与作为囊泡运输核心调控因子的Rab家族鸟苷三磷酸酶（Rab family GTPases）的相互作用相关。此前已有研究证实，这类GTP酶中的Rab1、Rab5、Rab10及Rab11可调控树突分支的发育。本研究通过在da神经元中调控Rab5、Rab7及Rab11的活性，并结合Mon1突变体开展遗传上位性（genetic epistasis）实验，证实Mon1对树突分支的调控作用可能源于其对循环运输通路（recycling pathway）的影响。树突分支对于神经元的正常连接及生理功能至关重要，正如本研究所揭示的，对Mon1这类调控元件的解析，对于理解神经元的功能机制具有不可或缺的意义。