TOR Complex 2 Integrates Cell Movement during Chemotaxis and Signal Relay in Dictyostelium

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.
Molecular Biology of the Cell (Impact Factor: 4.47). 11/2005; 16(10):4572-83. DOI: 10.1091/mbc.E05-04-0342
Source: PubMed


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.

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Available from: Koichi Okumura
    • "The mTORC2 complex, in contrast, is less well characterized. Evidence from D. melanogaster, Dictyostelium discoideum, and human cells suggest that mTORC2 responds to insulin and Ras signaling (Lee et al. 2005; Sarbassov et al. 2005; Charest et al. 2010), but its precise mechanism of activation remains elusive. mTORC2 regulates the activity of several substrates involved in cytoskeleton reorganization and cell polarity, but "
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    • "Pia is a component of the target of rapamycin complex 2 (TORC2) [40]. TORC2 plays roles in activation of ACA and PKB [40]–[43]. By reconstitution experiments using cells lacking both CRAC and Pia, it has shown that both CRAC and Pia are absolutely required for ACA activity [35]. "
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    • "Cyclic-AMP–induced blebbing depends on the single G protein encoded in the genome (Wu et al., 1995), but surprisingly, elimination of many proteins considered central to chemotaxis has no effect (Fig. S1 and Table S1). These include components of the TORC2 complex (Lee et al., 2005), the AKT homologue PKB (Meili et al., 1999; see later), the phospholipases PLA2 (Chen et al., 2007) and PLC (Kortholt et al., 2007), and the MAP kinase ERK2 (Segall et al., 1995). Calcium signaling is important for blebbing in zebrafish germ cells (Blaser et al., 2006), but eliminating chemotactic calcium signaling in Dictyostelium by knockout of the presumed IP 3 receptor, IplA (Traynor et al., 2000), has no discernable effect on blebbing. "
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