TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium
TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium
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DOI：
10.1091/mbc.e05-04-0342
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Firtel, RA
中科院分区：
文献类型：
--
作者：
Lee, S;Comer, FI;Firtel, RA
网骨藻细胞通过独立细胞的聚集形成多细胞生物体。该过程需要趋化性和信号传递，其中化学引诱物cAMP通过G蛋白偶联的cAMP受体cAR 1激活腺苷酸环化酶。cAMP被产生和分泌，并且它激活邻近细胞上的受体，从而将化学引诱物信号传递到远处的细胞。使用免疫共沉淀和质谱分析，我们已经确定了一个TOR-含有复杂的Dictyosteoblastoma的相关的TORC 2复杂的酿酒酵母和调节趋化性和信号中继。我们证明，在Dictyosteoblasts LST 8，RIP 3和Pia，直系同源的酵母TORC 2组件LST 8，AVO 1和AVO 3的突变，表现出一组共同的表型，包括减少细胞极性，趋化速度和方向性，Akt/PKB和相关的PKBR 1的磷酸化，和腺苷酸环化酶的激活。此外，我们提供的证据Ras在调节TORC 2的作用。我们建议，通过调节趋化性和信号中继，TORC 2起着至关重要的作用，在控制聚集协调的两个重要的武器的发展途径，导致多细胞的Dictyosteopathy。
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.