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Fig. 4 | Molecular Brain

Fig. 4

From: Disrupted-in-schizophrenia 1 (DISC1) and Syntaphilin collaborate to modulate axonal mitochondrial anchoring

Fig. 4

DISC1-MIRO-SNPH complex mediates the neuronal activation-induced mitochondrial anchoring. a Mitochondrial movement response upon neuronal activation. Primary cortical neurons were transfected as indicated followed by time-lapse imaging before and after treatment of 100 mM KCl for 5 min at DIV 10. i) Representative kymographs and ii) quantitative analyses (n = 30 axons, 332 mitochondria for control, n = 30 axons, 360 mitochondria for FLAG-mDISC1, n = 30 axons, 319 mitochondria for FLAG-mMIRO, n = 31 axons, 341 mitochondria for FLAG-mDISC1 and FLAG-mMIRO, n = 30 axons, 335 mitochondria for mSNPH-Myc, and n = 30 axons, 332 mitochondria for FLAG-mMIRO and mSNPH-Myc). Error bars are mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, NS, not significant, by one-way ANOVA with Bonferroni’s multiple comparison test. Scale bar; 10 μm. b Decreased association between SNPH and MIRO in the presence of DISC1. c Increased association between SNPH and MIRO in the DISC1 knockdown. Lysates from CAD cells transfected as indicated were subjected to immunoprecipitation followed by western blotting. In the western blot, the asterisk indicates the endogenous DISC1. Error bars are mean ± SEM. *P < 0.05, **P < 0.01, NS, not significant, by student’s t-test. d A schematic model for the roles of DISC1 in the mitochondrial motility. The association of DISC1 to SNPH inhibits the mitochondrial anchoring activity of SNPH, which facilitates the mitochondrial movement. The association between MIRO and SNPH is increased upon DISC1 deficiency, resulting in SNPH-mediated mitochondrial anchoring

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