<i>Chlamydomonas</i>
            Immunophilins and Parvulins: Survey and Critical Assessment of Gene Models

Vallon, Olivier

doi:10.1128/ec.4.2.230-241.2005

Cited by 42 publications

(42 citation statements)

References 37 publications

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“…We have identified and characterized two components of TOR signaling in Chlamydomonas, the TOR kinase and the FKBP12 immunophilin, which we will refer to as FKB12, as previously proposed for this alga (Vallon, 2005). Our findings indicate that rapamycin inhibits growth of Chlamydomonas cells.…”

supporting

confidence: 53%

“…Similar to other immunophilins, FKBP12 has peptidyl prolyl cis/trans isomerase activity that is involved in protein-folding processes. Studies have identified FKBP12 in bacteria, fungi, animals, plants (for review, see Schreiber, 1991;Fruman et al, 1994;He et al, 2004), and more recently in the green alga Chlamydomonas reinhardtii (Vallon, 2005). However, the physiological function of this protein is still poorly understood.…”

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confidence: 99%

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Inhibition of Target of Rapamycin Signaling by Rapamycin in the Unicellular Green Alga Chlamydomonas reinhardtii

2005

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The macrolide rapamycin specifically binds the 12-kD FK506-binding protein (FKBP12), and this complex potently inhibits the target of rapamycin (TOR) kinase. The identification of TOR in Arabidopsis (Arabidopsis thaliana) revealed that TOR is conserved in photosynthetic eukaryotes. However, research on TOR signaling in plants has been hampered by the natural resistance of plants to rapamycin. Here, we report TOR inactivation by rapamycin treatment in a photosynthetic organism. We identified and characterized TOR and FKBP12 homologs in the unicellular green alga Chlamydomonas reinhardtii. Whereas growth of wild-type Chlamydomonas cells is sensitive to rapamycin, cells lacking FKBP12 are fully resistant to the drug, indicating that this protein mediates rapamycin action to inhibit cell growth. Unlike its plant homolog, Chlamydomonas FKBP12 exhibits high affinity to rapamycin in vivo, which was increased by mutation of conserved residues in the drugbinding pocket. Furthermore, pull-down assays demonstrated that TOR binds FKBP12 in the presence of rapamycin. Finally, rapamycin treatment resulted in a pronounced increase of vacuole size that resembled autophagic-like processes. Thus, our findings suggest that Chlamydomonas cell growth is positively controlled by a conserved TOR kinase and establish this unicellular alga as a useful model system for studying TOR signaling in photosynthetic eukaryotes.The macrolide antibiotic rapamycin is a product of the bacterium Streptomyces hygroscopicus. Rapamycin was originally identified as a potent antifungal agent (Vezina et al., 1975) and much later was found to exhibit immunosuppressive activity due to its capacity to block the growth and proliferation of T cells (Schreiber, 1992;Sigal and Dumont, 1992). More recently, rapamycin has been found to display anticancer properties (Bjornsti and Houghton, 2004).Rapamycin inhibits cell growth in many types of cells, including the budding yeast Saccharomyces cerevisiae. Studies performed in yeasts uncovered the unique mechanism of action of rapamycin. Both receptor and functional target were initially identified in S. cerevisiae (Heitman et al., 1991). Rapamycin first binds the 12-kD FK506-binding protein (FKBP12) and this complex inhibits the target of rapamycin (TOR) Ser/Thr kinase. FKBP12 is a member of the FK506-and rapamycin-binding protein (FKBP) family. This group of proteins, together with the cyclosporin A receptors, is collectively referred to as immunophilins because of their ability to tightly bind the immunosuppressive drugs rapamycin, FK506, or cyclosporin A (Schreiber, 1991;Fruman et al., 1994). Similar to other immunophilins, FKBP12 has peptidyl prolyl cis/trans isomerase activity that is involved in protein-folding processes. Studies have identified FKBP12 in bacteria, fungi, animals, plants (for review, see Schreiber, 1991;Fruman et al., 1994;He et al., 2004), and more recently in the green alga Chlamydomonas reinhardtii (Vallon, 2005). However, the physiological function of this protein is still poorly understood....

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supporting

confidence: 53%

mentioning

confidence: 99%

Inhibition of Target of Rapamycin Signaling by Rapamycin in the Unicellular Green Alga Chlamydomonas reinhardtii

2005

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“…2D). Parallel immunoblot assays with antisera specific to D1, a chloroplast membrane protein, to COXIIb, a mitochondrial membrane protein, or to CrFKBP12, a cytoplasmic soluble protein (9,51), showed that the microsome-containing fraction is not significantly contaminated with thylakoidal and mitochondrial membranes or soluble cytoplasmic proteins (Fig. 2D).…”

Section: Tor-interacting Proteins Inmentioning

confidence: 99%

Target of Rapamycin and LST8 Proteins Associate with Membranes from the Endoplasmic Reticulum in the Unicellular Green Alga Chlamydomonas reinhardtii

2008

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The highly conserved target of rapamycin (TOR) kinase is a central controller of cell growth in all eukaryotes. TOR exists in two functionally and structurally distinct complexes, termed TOR complex 1 (TORC1) and TORC2. LST8 is a TOR-interacting protein that is present in both TORC1 and TORC2. Here we report the identification and characterization of TOR and LST8 in large protein complexes in the model photosynthetic green alga Chlamydomonas reinhardtii. We demonstrate that Chlamydomonas LST8 is part of a rapamycin-sensitive TOR complex in this green alga. Biochemical fractionation and indirect immunofluorescence microscopy studies indicate that TOR and LST8 exist in high-molecular-mass complexes that associate with microsomal membranes and are particularly abundant in the peri-basal body region in Chlamydomonas cells. A Saccharomyces cerevisiae complementation assay demonstrates that Chlamydomonas LST8 is able to functionally and structurally replace endogenous yeast LST8 and allows us to propose that binding of LST8 to TOR is essential for cell growth.The Ser/Thr kinase target of rapamycin (TOR) is a central regulator of cell growth and metabolism in all eukaryotes (recently reviewed by Wullschleger et al. [54]). Studies of TOR signaling in yeast and mammals have demonstrated that TOR controls cell growth in response to nutrients and different stresses (10, 54). The TOR kinases are large (about 270 kDa) proteins that assemble into two structurally and functionally distinct multisubunit complexes of 1.5 to 2.0 MDa termed TOR complex 1 (TORC1) and TORC2. The similar composition of TORCs in widely divergent kingdoms such as metazoans and fungi suggests that these complexes are broadly conserved across all eukaryotes. The two TORCs were initially identified in yeast (34, 52) and subsequently in mammals (18,23,26,44). In yeast, TORC1 contains either TOR1 or TOR2, KOG1, TCO89, and LST8, whereas TORC2 includes TOR2 (but not TOR1), LST8, BIT61, AVO1, AVO2, and AVO3 (34, 41, 52). Mammalian TOR (mTOR) associates with raptor (homologue of yeast KOG1) and mLST8 to constitute mTORC1, while mTORC2 consists of mLST8, rictor (homologue of yeast AVO3), hSIN1 (homologue of yeast AVO1), and mTOR (15,18,22,23,27,34,44,57). With the exception of the yeast proteins TCO89, BIT61, and AVO2, all TOR partners are essential for growth of yeast and mammalian cells (16,34,42).Studies performed in yeast and mammalian cells demonstrate that TORC1 mediates the rapamycin-sensitive signaling branch that regulates translation, ribosome biogenesis, autophagy, and nitrogen and carbon degradative pathways (54). Some of these readouts are mediated via the AGC kinases S6K1 (mammals) and Sch9 (yeast), which are phosphorylated and thus activated by TORC1 (4, 21, 50). TORC2, on the other hand, is insensitive to rapamycin and controls actin cytoskeleton organization (23,34,44), presumably via its direct AGC kinase substrates Akt/PKB (mammals) and YPK1/2 (yeast) (24,36,45). Recently, it has been reported that TORC1 and TORC2 are multimeric supercomplexes...

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“…This study also uncovered a unique and previously uncharacterized domain, which may provide further understanding of the auto-inhibition mechanism of CYP38 function [36]. There are more than 50 gene models in Chlamydomonas with similarity to immunophilin proteins [75]. However, their possible functions in PSII assembly await further investigation.…”

Section: Regulatory Factors For Psii Assemblymentioning

confidence: 99%

Regulatory factors for the assembly of thylakoid membrane protein complexes

Chi

Zhang

2012

Phil. Trans. R. Soc. B

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Major multi-protein photosynthetic complexes, located in thylakoid membranes, are responsible for the capture of light and its conversion into chemical energy in oxygenic photosynthetic organisms. Although the structures and functions of these photosynthetic complexes have been explored, the molecular mechanisms underlying their assembly remain elusive. In this review, we summarize current knowledge of the regulatory components involved in the assembly of thylakoid membrane protein complexes in photosynthetic organisms. Many of the known regulatory factors are conserved between prokaryotes and eukaryotes, whereas others appear to be newly evolved or to have expanded predominantly in eukaryotes. Their specific features and fundamental differences in cyanobacteria, green algae and land plants are discussed.

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Chlamydomonas Immunophilins and Parvulins: Survey and Critical Assessment of Gene Models

Cited by 42 publications

References 37 publications

Inhibition of Target of Rapamycin Signaling by Rapamycin in the Unicellular Green Alga Chlamydomonas reinhardtii

Inhibition of Target of Rapamycin Signaling by Rapamycin in the Unicellular Green Alga Chlamydomonas reinhardtii

Target of Rapamycin and LST8 Proteins Associate with Membranes from the Endoplasmic Reticulum in the Unicellular Green Alga Chlamydomonas reinhardtii

Regulatory factors for the assembly of thylakoid membrane protein complexes

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