RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1.大型树突分支结构的构建需要稳健的生长过程，并将膜与蛋白质货物精准递送至发育中树突的特定亚细胞区域。目前，学界对如何调控基于微管的囊泡运输与分选系统，以将这类树突发育因子分布至整个树突的机制仍不甚明晰。本研究鉴定出小GTP酶RAB-10（small GTPase RAB-10）与胞泌复合体（exocyst complex），二者是秀丽隐杆线虫（C. elegans）感觉神经元PVD中树突形态发生与模式建成的关键调控因子。在rab-10基因突变体中，PVD神经元的树突分支在细胞后侧区域显著减少，但在细胞远端前侧区域却过度增生。本研究同时证实，PVD神经元内的树突分支分布依赖于分子驱动蛋白kinesin-1/UNC-116与动力蛋白dynein之间的动态平衡，并提出RAB-10通过平衡这两类驱动蛋白的活性，以合理分配包括跨膜受体DMA-1在内的分支形成因子，进而调控树突形态。