Spatial control of nucleoporin assembly by Fragile X-related proteins
biorxiv(2019)
摘要
Nucleoporins (Nups) build highly organized Nuclear Pore Complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs to regulate nucleocytoplasmic exchange. In the cytoplasm, a large excess of soluble Nups has been reported, but how their assembly is restricted to the NE is currently unknown. Here we show that Fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule and dynein-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and Fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup protein condensates. Likewise, several models of Fragile X syndrome (FXS), characterized by a loss of FMRP, also accumulate cytoplasmic Nup aggregates. These aggregate-containing cells display aberrant nuclear morphology and a delay in G1 cell cycle progression. Our results reveal an unexpected role for the FXR protein family and dynein in the spatial regulation of nucleoporin assembly.
更多查看译文
关键词
nucleoporins,phase separation,FMRP,FXR1,FXR2,Fragile X syndrome,dynein,microtubules,nucleus,G1
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要