Lee Susan, Comer Frank I, Sasaki Atsuo, McLeod Ian X, Duong Yung, Okumura Koichi, Yates John R, Parent Carole A, Firtel Richard A
Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093-0380, USA.
Mol Biol Cell. 2005 Oct;16(10):4572-83. doi: 10.1091/mbc.e05-04-0342. Epub 2005 Aug 3.
Dictyostelium cells form a multicellular organism through the aggregation of independent cells. This process requires both chemotaxis and signal relay in which the chemoattractant cAMP activates adenylyl cyclase through the G protein-coupled cAMP receptor cAR1. cAMP is produced and secreted and it activates receptors on neighboring cells, thereby relaying the chemoattractant signal to distant cells. Using coimmunoprecipitation and mass spectrometric analyses, we have identified a TOR-containing complex in Dictyostelium that is related to the TORC2 complex of Saccharomyces cerevisiae and regulates both chemotaxis and signal relay. We demonstrate that mutations in Dictyostelium LST8, RIP3, and Pia, orthologues of the yeast TORC2 components LST8, AVO1, and AVO3, exhibit a common set of phenotypes including reduced cell polarity, chemotaxis speed and directionality, phosphorylation of Akt/PKB and the related PKBR1, and activation of adenylyl cyclase. Further, we provide evidence for a role of Ras in the regulation of TORC2. We propose that, through the regulation of chemotaxis and signal relay, TORC2 plays an essential role in controlling aggregation by coordinating the two essential arms of the developmental pathway that leads to multicellularity in Dictyostelium.
盘基网柄菌细胞通过独立细胞的聚集形成多细胞生物体。这个过程既需要趋化作用也需要信号传递，其中趋化因子cAMP通过G蛋白偶联的cAMP受体cAR1激活腺苷酸环化酶。cAMP产生并分泌，它激活邻近细胞上的受体，从而将趋化因子信号传递给远处的细胞。利用免疫共沉淀和质谱分析，我们在盘基网柄菌中鉴定出一种含TOR的复合物，它与酿酒酵母的TORC2复合物相关，并调节趋化作用和信号传递。我们证明，盘基网柄菌中酵母TORC2组分LST8、AVO1和AVO3的直系同源物LST8、RIP3和Pia的突变表现出一组共同的表型，包括细胞极性降低、趋化速度和方向性降低、Akt/PKB和相关PKBR1的磷酸化以及腺苷酸环化酶的激活。此外，我们提供了Ras在TORC2调节中起作用的证据。我们提出，通过对趋化作用和信号传递的调节，TORC2通过协调导致盘基网柄菌多细胞性的发育途径的两个重要分支，在控制聚集过程中发挥重要作用。
