Evaluating LRRK2 Genetic Variants with Unclear Pathogenicity

Figure 2

Impact of LRRK2 wild-type and mutants on basal cell survival and survival in response to H₂O₂ insult in HEK 293T cells and their corresponding kinase activities. (a) Changes in percentage cell survival between cells expressing LRRK2 wild-type and mutants from LRR (L1165P), ROC (T1410M), COR (M1646T), kinase (L2063X), and WD40 (Y2189C) domains, shown in response to 500 μM H₂O₂ for 24 hours. (b) Autokinase activity of the wild-type and mutants in RLU measured using the Transcreener ADP² FI Assay. (c) Correlation between autokinase activity and percentage cell survival. Data are means ± standard error of the mean (SEM), three readings per data point, from at least 3 independent experiments. Two-tailed Student’s t-test; ^# and versus percentage change in cell survival in cell expressing LRRK2 mutants with respect to the wild-type, in the presence and absence of H₂O₂, respectively; versus kinase activity with respect to wild-type LRRK2.

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