The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ and R7-RGS-binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of G α-subunits, several neurological phenotypes of R7-RGS knock-out mice are not readily explained by dysregulated G signaling. Accordingly, we used tandem affinity purification and LC-MS/MS to search for novel proteins that interact with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we focused on Gα because it had not been linked to R7-RGS complexes before. Split-luciferase complementation assays indicated that Gα in its active or inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform. LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between activated Gα and R7-RGS heterotrimers, indicating that these effector RhoGEFs can engage Gα·R7-RGS complexes. Because Gα/R7-RGS interaction required R7BP, we analyzed phenotypes of neuronal cell lines expressing RGS7 and Gβ with or without R7BP. We found that neurite retraction evoked by Gα-dependent lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP expression blunted neurite formation evoked by serum starvation by signaling mechanisms involving Gα but not Gα These findings provide the first evidence that R7-RGS heterotrimers interact with Gα to augment signaling pathways that regulate neurite morphogenesis. This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function.
John Brown, author of Slave Life in Georgia, published in London in 1854, proffered a radical approach to ending slavery in the United States in step with, if not premised upon, Marx. In this paper, we will draw attention to Brown's nearly forgotten narrative, explaining how its model of subjectivity may in part explain its neglect. Brown treats freedom as something foreign and external. He has to learn what freedom means, first through exposure to a model of liberal citizenship -this offered by a free Afro-Briton abandoned to slave sellers in Charleston, SC -and then through the experience of several modulations of fugitive liberty.Enslaved or free, Brown's social world is wholly determined by external forces and material conditions. Whether slave or freeman, he faces ambiguous situations. Is one master better than another? Will he join a community of fugitive slaves in Indiana? Will he seek refuge from slavery as a laborer in a copper mine? Will he accompany a patron to England? Brown's hesitancy at each of these modalities of freedom takes him also further north, where he serves as a carpenter among fugitives in Canada West. These model communities, designed under the purview of white benefactors to showcase how freed slaves could overcome degradation, also ultimately displease Brown. His postponed travel to England is at last resumed, where he takes up a new charge: Brown proposes a systematic attack on the economic conditions that support the slaveocracy. His goal will be to undersell southern cotton and dismantle southern 1 mdrexler@bucknell.edu 2 economy through competition. Despite his failure to execute his design, Brown remains an important voice, one committed to systemic change through interventional labor practices, rather than moral suasion through sentimental identification. TEXTBy the middle of the 19 th Century, white abolitionists had fully embraced fugitive slave narratives as powerful devices of moral suasion. The narratives' vivid accounts of cruelty, including the separation of families and methods of torture, would, they believed, evoke sympathy and generate support from recalcitrant white northerners. However, the genre had also been, since its inception, a broad canvas for demonstrating black agency, recording cultural practices, describing farming techniques, and showcasing intellectual as well as physical accomplishments. These fugitive slave authors did not abandon such motivations, even after the unprecedented success of Harriet Beecher Stowe's sentimentalized anti-slavery fiction led writers to revise their literary strategies. Nor did fugitive slave narrators universally embrace any one approach to combatting slavery as an institution. In this paper, we will draw attention to one narrator's materialist critique of cotton production that leads him to advocate for dismantling slavery by rendering the southern economy profitless; but before turning to John Brown and his book Slave Life in Georgia, we offer an astonishing coincidence where Brown's story intersects with the more famous a...
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