PDF(Pubmed)
Abstract：
The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.
摘要：
视网膜有精美的图案，神经元躯体定期定位以完全采样视野。这里,我们表明磷酸酶和张力蛋白同源物（Pten）通过调节细胞粘附分子和Wnt蛋白的囊泡运输来控制星爆无长突细胞间距。单细胞转录组学和双突变体分析显示，Pten和Down综合征细胞粘附分子Dscam）共表达并附加作用于星状无长突细胞镶嵌。机械上,Pten丢失加速了DSCAM的内吞运输，FAT3和MEGF10脱离细胞膜并进入无长突细胞的内吞囊泡。因此，囊泡蛋白质组，细胞起源的分子特征，富含胞吐作用，囊泡介导的转运，和Pten条件性敲除（PtencKO）视网膜中的受体内化蛋白。Wnt信号分子也富集在PtencKO视网膜囊泡中，和Wnt信号表型的遗传或药理学破坏无长突细胞模式缺陷。因此，Pten控制细胞粘附和信号分子的囊泡运输，以建立视网膜无长突细胞镶嵌。
