ニューロン樹状突起発達過程のアクチン動態を制御するＭＴＳＳ１の機能解析

使用MTSS1敲除浦肯野细胞（PC）的时移成像测量的参数，我进行了计算机模拟，以模拟树突突起长度增加的影响，并观察到所得的树突表型与真实的PC相似。我进一步表明，MTSS1和DAAM1都共定位在浦肯野细胞的树突状突起的尖端。使用TIRF显微镜，我观察到MIM抑制DAAM 1肌动蛋白聚合活性，并且使用西姆斯成像也可以在细胞中看到这种负调控。在浦肯野细胞中诱导DAAM1的组成型活性表达导致丝状伪足长度增加，类似于我们的MTSS1突变体表型，表明MTSS1抑制DAAM1在发育树突状突起中的活性。

Using parameters measured from timelapse imaging of MTSS1 knockout Purkinje cells (PCs), I performed a computer simulation to model the effect of increased dendritic protrusion length and observed that the resulting dendritic phenotype was similar to real PCs. I further showed that both MTSS1 and DAAM1 are colocalized at the tips of dendritic protrusions in Purkinje cells. Using TIRF microscopy, I observed that MIM inhibits DAAM1 actin-polymerizing activity, and could also see this negative regulation in cells using SiMS imaging. Induced constitutive active expression of DAAM1 in Purkinje cells resulted in increased filopodia length, similar to our MTSS1 mutant phenotype, suggesting MTSS1 inhibits the activity of DAAM1 in developing dendritic protrusions.