Transmembrane Receptor DCC Associates with Protein Synthesis Machinery and Regulates Translation

Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell (Impact Factor: 32.24). 05/2010; 141(4):632-44. DOI: 10.1016/j.cell.2010.04.008
Source: PubMed


Extracellular signals regulate protein translation in many cell functions. A key advantage of control at the translational level is the opportunity to regulate protein synthesis within specific cellular subregions. However, little is known about mechanisms that may link extracellular cues to translation with spatial precision. Here, we show that a transmembrane receptor, DCC, forms a binding complex containing multiple translation components, including eukaryotic initiation factors, ribosomal large and small subunits, and monosomes. In neuronal axons and dendrites DCC colocalizes in particles with translation machinery, and newly synthesized protein. The extracellular ligand netrin promoted DCC-mediated translation and disassociation of translation components. The functional and physical association of a cell surface receptor with the translation machinery leads to a generalizable model for localization and extracellular regulation of protein synthesis, based on a transmembrane translation regulation complex.

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Available from: Joseph Tcherkezian, May 20, 2014
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    • "The mechanisms of RNA localization, translation, and stability are coupled, and it is common for individual RNA-binding proteins to influence more than one of these processes (Dreyfuss et al., 2002). Other aspects that might be interesting for future investigation are the potential relationship with previously described RNA granules (Xing and Bassell, 2013; Yasuda et al., 2013), or cellsurface receptors (Tcherkezian et al., 2010), and whether APC is part of a constitutive mechanism of the growth cone machinery or might be regulated by extracellular cues. Besides its function as a cytoskeletal regulator, APC is well known as a component of the Wnt/b-catenin pathway, where it binds and regulates the degradation of b-catenin protein (Clevers and Nusse, 2012). "
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    • "At least one study directly addressed this question. Flanagan and colleagues showed that deleted in colorectal cancer-1 (DCC1), a single transmembrane cell-surface receptor for netrin-1, directly binds to ribosomes and translation initiation factors, and translation is promoted by ligand binding (Tcherkezian et al., 2010). As ribosomes and initiation factors are components of mRNPs such as stress granules (Erickson and Lykke-Andersen, 2011), their interaction with cellsurface receptors, which can be regulated by ligand-receptor interaction, provides a conceptually appealing mechanism of cue-mRNA specificity. "
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    • "The machinery for protein synthesis localized in the axonal periphery may be organized and regulated in a distinct manner that is strikingly different from that in the cell body. According to a recent article (Tcherkezian et al., 2010), the growth cone netrin receptor called " deleted in colorectal carcinoma (DCC) " is physically associated with elements of the protein synthetic machinery such as monosomes, "
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