Fig. 4: The R702W substitution changes the subcellular distribution of SorCS2 processed isoforms. | Molecular Psychiatry

Fig. 4: The R702W substitution changes the subcellular distribution of SorCS2 processed isoforms.

From: A low frequency damaging SORCS2 variant identified in a family with ADHD compromises receptor stability and quenches activity

Fig. 4

A representative western blot of sucrose gradient centrifugation of HEK293T cells transfected with SorCS2 WT or R702W. B quantification of A shows the level of SorCS2 processed forms in each fraction as percentage to total SorCS2 for WT or R702W SorCS2 (mean ± SEM, n = 3–4, statistical analysis by paired two tailed Student’s t test, *=p ≤ 0.05, **=p ≤ 0.01, ***=p ≤ 0.001). C surface proteins in HEK293T cells transfected with WT or R702W SorCS2 were biotinylated on ice and biotinylated SorCS2 precipitated with streptavidin (P). Non-precipitable SorCS2 (NP) represents intracellular SorCS2. Whereas a fraction of SorCS2 WT localizes to the cell surface, SorCS2 R702W is mainly found intracellularly. Precipitation of biotinylated endogenous insulin receptor (lower western blot) demonstrates that samples are biotinylated and precipitated equally well. Shown is mean ± SEM (n = 6). Statistical analysis by paired two tailed Student’s t test. D semi-quantitative RT-PCR showing increased expression of GRP78 in HEK293T cells when transfected with SorCS2 R702W relative to WT. Data shown as mean ± SEM (n = 3). Data analyzed by unpaired two tailed Student’s t test.

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