Department of Biology, Stanford University, Stanford, California, USA.
PLoS One. 2013;8(3):e58589. doi: 10.1371/journal.pone.0058589. Epub 2013 Mar 12.
Centriolar satellites are proteinaceous granules that are often clustered around the centrosome. Although centriolar satellites have been implicated in protein trafficking in relation to the centrosome and cilium, the details of their function and composition remain unknown. FOP (FGFR1 Oncogene Partner) is a known centrosome protein with homology to the centriolar satellite proteins FOR20 and OFD1. We find that FOP partially co-localizes with the satellite component PCM1 in a cell cycle-dependent manner, similarly to the satellite and cilium component BBS4. As for BBS4, FOP localization to satellites is cell cycle dependent, with few satellites labeled in G1, when FOP protein levels are lowest, and most labeled in G2. FOP-FGFR1, an oncogenic fusion that causes a form of leukemia called myeloproliferative neoplasm, also localizes to centriolar satellites where it increases tyrosine phosphorylation. Depletion of FOP strongly inhibits primary cilium formation in human RPE-1 cells. These results suggest that FOP is a centriolar satellite cargo protein and, as for several other satellite-associated proteins, is involved in ciliogenesis. Localization of the FOP-FGFR1 fusion kinase to centriolar satellites may be relevant to myeloproliferative neoplasm disease progression.
中心体卫星是蛋白质颗粒,通常聚集在中心体周围。虽然中心体卫星与中心体和纤毛的蛋白质运输有关,但它们的功能和组成细节仍不清楚。FOP(FGFR1 癌基因伙伴)是一种已知的中心体蛋白,与中心体卫星蛋白 FOR20 和 OFD1 具有同源性。我们发现,FOP 与卫星成分 PCM1 以细胞周期依赖性的方式部分共定位,类似于卫星和纤毛成分 BBS4。与 BBS4 一样,FOP 定位于卫星的位置是细胞周期依赖性的,在 G1 期标记的卫星较少,此时 FOP 蛋白水平最低,而在 G2 期标记的卫星较多。FOP-FGFR1 是一种致癌融合基因,可导致一种称为骨髓增生性肿瘤的白血病,它也定位于中心体卫星,在那里它增加酪氨酸磷酸化。FOP 的耗竭强烈抑制人 RPE-1 细胞中初级纤毛的形成。这些结果表明,FOP 是一种中心体卫星货物蛋白,与其他几种卫星相关蛋白一样,参与纤毛发生。FOP-FGFR1 融合激酶定位于中心体卫星可能与骨髓增生性肿瘤疾病进展有关。