Harish Rohit Krishnan, Tendulkar Shweta, Deivasigamani Senthilkumar, Ratnaparkhi Anuradha, Ratnaparkhi Girish S
Indian Institutes of Science Education and Research, Pune, India.
Agharkar Research Institute, Pune, India.
Front Cell Dev Biol. 2019 Aug 2;7:145. doi: 10.3389/fcell.2019.00145. eCollection 2019.
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 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.
莫能菌素敏感蛋白1（Mon1）是Mon1:Ccz1复合物的一个组成部分，在囊泡运输过程中，它作为Rab7的鸟嘌呤核苷酸交换因子，介导真核细胞中Rab5向Rab7的转化。我们发现，在幼虫发育过程中，Mon1的活性调节IV类树突分支（da）神经元的复杂性。Mon1功能的丧失会导致分支和复杂性增加，而其表达增加则会导致分支减少。Mon1影响树突发育的能力可能是其与Rab家族GTP酶相互作用的结果，这些GTP酶是囊泡运输的核心参与者。此前，这些GTP酶，特别是Rab1、Rab5、Rab10和Rab11已被证明可调节树突分支。我们通过调节da神经元、突变体中Rab5、Rab7和Rab11的活性，进行了基因上位性实验，并证明Mon1调节分支的能力可能是由于其对再循环途径的影响。树突分支对于神经元的正常连接和生理功能至关重要。如我们的研究所表明的，了解诸如Mon1等调节元件对于理解神经元功能至关重要。
