Factors controlling fibroblast growth factor receptor-1's cytoplasmic trafficking and its regulation as revealed by FRAP analysis
Factors controlling fibroblast growth factor receptor-1's cytoplasmic trafficking and its regulation as revealed by FRAP analysis
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DOI：
10.1091/mbc.e05-08-0749
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Stachowiak, MK
中科院分区：
文献类型：
--
作者：
Dunham-Ems, SM;Pudavar, HE;Stachowiak, MK
生物化学和显微镜研究表明，FGFR 1是一种跨膜可溶性蛋白，存在于细胞质和细胞核中。FGFR 1如何进入细胞质并随后进入细胞核以控制细胞发育和相关基因活性已成为一个引人注目的问题。对FGFR 1-EGFP和FGFR 1突变体的蛋白质合成、细胞质亚区室分布和运动的分析表明，FGFR 1以三个独立的群体存在：（a）新合成的、高度移动的、非糖基化的胞质受体，其被布雷菲德菌素A耗尽并位于ER-高尔基体腔外;（B）缓慢扩散的膜受体群体;和（c）由布雷菲德菌素A增加的非移动的膜池。RSK 1增加了高度移动的细胞溶质FGFR 1群体及其总体扩散速率，导致FGFR 1核蓄积增加，其与RSK 1共蓄积。提出了一种模型，其中新合成的FGFR 1可以进入（a）“核途径”，其中非糖基化受体从前高尔基体中挤出，产生高度移动的胞质受体分子，这些分子在核中快速积累，或（B）“膜途径”，其中FGFR 1通过高尔基体加工，其中其移动在空间上限于具有有限横向移动性的跨高尔基体膜。FGFR 1与激酶活性RSK 1的相互作用有利于进入核途径。
Biochemical and microscopic studies have indicated that FGFR1 is a transmembrane and soluble protein present in the cytosol and nucleus. How FGFR1 enters the cytosol and subsequently the nucleus to control cell development and associated gene activities has become a compelling question. Analyses of protein synthesis, cytoplasmic subcompartmental distribution and movement of FGFR1-EGFP and FGFR1 mutants showed that FGFR1 exists as three separate populations (a) a newly synthesized, highly mobile, nonglycosylated, cytosolic receptor that is depleted by brefeldin A and resides outside the ER-Golgi lumen, (b) a slowly diffusing membrane receptor population, and (c) an immobile membrane pool increased by brefeldin A. RSK1 increases the highly mobile cytosolic FGFR1 population and its overall diffusion rate leading to increased FGFR1 nuclear accumulation, which coaccumulates with RSK1. A model is proposed in which newly synthesized FGFR1 can enter the (a) "nuclear pathway," where the nonglycosylated receptor is extruded from the pre-Golgi producing highly mobile cytosolic receptor molecules that rapidly accumulate in the nucleus or (b) "membrane pathway," in which FGFR1 is processed through the Golgi, where its movement is spatially restricted to trans-Golgi membranes with limited lateral mobility. Entrance into the nuclear pathway is favored by FGFR1's interaction with kinase active RSK1.