Lysosomal
Akt/mTORC1 signaling activities are dependent on endocytosis.
(a) Average time courses of normalized excitation ratio (R: Ex480/405)
in serum-starved NIH3T3 cells expressing lysosome-targeted ExRai-AktAR2
(Lyso-ExRai-AktAR2) stimulated with 50 ng/mL of PDGF without (green, n = 16) or with 50 μM Dyngo-4a pretreatment for 10
min (gray, n = 20). (b) Responses of Lyso-ExRai-AktAR2
in PDGF-treated serum-starved NIH3T3 cells without (n = 16) or with pretreatment of Dyngo-4a (n = 20).
****, P < 0.0001; unpaired two-tailed Student’s t test with Welch’s correction. (c) Pearson correlation
coefficient (PCC) analysis of Akt and lysosome colocalization in serum-starved
NIH3T3 cells without (gray triangle) or with PDGF stimulation (red
triangle) in the absence or presence of 50 μM Dyngo-4a. In the
absence of Dyngo-4a: ***, P = 0.0006, – PDGF
vs + PDGF; In the presence of Dyngo-4a: ns, not significant, P = 0.94, – PDGF vs + PDGF; Without PDGF stimulation:
ns, not significant, P = 0.99, – Dyngo-4a
vs + Dyngo-4a; Ordinary one-way ANOVA followed by Tukey’s multiple
comparison test. (d) Mander’s overlap coefficient (MOC) analysis
of colocalization of Akt and the lysosome in serum-starved NIH3T3
cells without (gray dots) or with PDGF stimulation (red dots) in the
absence of presence of 50 μM Dyngo-4a. In the absence of Dyngo-4a:
***, P = 0.0003, – PDGF vs + PDGF; In the
presence of Dyngo-4a: ns, not significant, P = 0.96,
– PDGF vs + PDGF; Without PDGF stimulation: ns, not significant, P = 1.0, – Dyngo-4a vs + Dyngo-4a; Ordinary one-way
ANOVA followed by Tukey’s multiple comparison test. (e) Domain
structure of lysosome-targeted TORCAR (Lyso-TORCAR). (f) Average time
courses of normalized emission ratio (cyan/yellow) in serum-starved
NIH3T3 cells expressing Lyso-TORCAR stimulated with 50 ng/mL of PDGF
without (blue, n = 11) or with 50 μM Dyngo-4a
pretreatment for 10 min (gray, n = 18). (g) Responses
of Lyso-TORCAR in PDGF-treated serum-starved NIH3T3 cells without
(n = 11) or with pretreatment of Dyngo-4a (n = 18). ****, P < 0.0001; unpaired
two-tailed Student’s t test. Solid lines in
(a, f) indicate mean responses; shaded areas, SEM. Bars denote mean
± SEM (b–d, g).