(A) Representative fluorescence images from three independent experiments showing the localization of overexpressed constructs in NIH3T3 cells. Fluorescence of mCherry, mCherry-TSC2 and mCherry-TSC2-AA mutant are shown as “RFP”. “CFP” shows fluorescence of TORCAR. (B-C) Representative averaged time course traces (B) and summary (C) of PDGF-induced maximum responses of TORCAR in the cytosolic regions of double starved NIH3T3 cells. mCherry (blue, N = 27); mCherry-TSC2 (yellow, N = 35); mCherry-TSC2-AA (green, N = 32). (D) Model depicting lysosomal TSC2-dependent spatial regulation of mTORC1 activation. (E) Representative fluorescence images from three independent experiments showing the localization of overexpressed nuclearly targeted constructs in NIH3T3 cells. Fluorescence of mCherry-NLS, mCherry-TSC2-NLS and mCherry-TSC2-AA-NLS mutant are shown as “RFP”. “CFP” shows the fluorescence of TORCAR-NLS. (F-G) Representative averaged time course traces (F) and summary (G) of PDGF-induced maximum responses of TORCAR-NLS in double starved NIH3T3 cells. Co-expressed constructs: mCherry-NLS (blue, N = 20); mCherry-TSC2-NLS (yellow, N = 23); mCherry-TSC2-AA-NLS (green, N = 26). (H) Model depicting the inhibition of nuclear mTORC1 activity by overexpressed nuclear TSC2. N indicates the cell number quantified from at least 3 independent experiments. Shaded areas indicate standard error of the mean (SEM). Box plots show the upper and lower adjacent values, interquartile range and the median. Scale bar = 10 µm. See also Figure S2.