Blaauw Mieke, Knol Jaco C, Kortholt Arjan, Roelofs Jeroen, Postma Marten, Visser Antonie J W G, van Haastert Peter J M
Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
EMBO J. 2003 Oct 1;22(19):5047-57. doi: 10.1093/emboj/cdg508.
Retinal phosducin is known to sequester transducin Gbetagamma, thereby modulating transducin activity. Phosducin is a member of a family of phosducin-like proteins (PhLP) found in eukaryotes. Phylogeny of 33 phosducin-like proteins from metazoa, plants and lower eukaryotes identified three distinct groups named phosducin-I-III. We discovered three phlp genes in Dictyostelium, each encoding a phosducin-like protein of a different group. Disruption of the phlp1 gene strongly impaired G-protein signalling, apparently due to mislocalization of Gbetagamma in phlp1-null cells. GFP-Gbeta and GFP-Ggamma are membrane associated in wild-type cells, but cytosolic in phlp1-null cells. Phlp2 disruption is lethal due to a synchronous collapse of the cells after 16-17 cell divisions. Phlp3 disruptants show no abnormal phenotype. These results establish a role for phosducin-like proteins in facilitating folding, localization or function of proteins, in addition to modulating G-protein signalling.
已知视网膜磷光蛋白可隔离转导素Gβγ，从而调节转导素活性。磷光蛋白是真核生物中发现的一类磷光蛋白样蛋白（PhLP）家族的成员。对来自后生动物、植物和低等真核生物的33种磷光蛋白样蛋白进行系统发育分析，确定了三个不同的组，分别命名为磷光蛋白-I - III。我们在盘基网柄菌中发现了三个phlp基因，每个基因编码不同组的一种磷光蛋白样蛋白。phlp1基因的破坏严重损害了G蛋白信号传导，这显然是由于phlp1基因缺失细胞中Gβγ的定位错误所致。在野生型细胞中，GFP - Gβ和GFP - Gγ与膜相关，但在phlp1基因缺失细胞中位于胞质中。phlp2基因的破坏是致命的，因为在16 - 17次细胞分裂后细胞会同步崩溃。phlp3基因缺失突变体未表现出异常表型。这些结果表明，除了调节G蛋白信号传导外，磷光蛋白样蛋白在促进蛋白质的折叠、定位或功能方面也发挥作用。
