Fig. 1

Biochemical characterization of rare TREM2 variants identified at the UCSF Memory and Aging Center. a Seven rare TREM2 variants were transiently expressed in HEK-293T cells and compared to cells expressing wild type (WT) TREM2, the Y38C variant or untransfected cells (—). One day after transfection, cells were lysed and the lysates analyzed (in duplicate) by immunoblotting for TREM2 to assess expression, maturation, and electrophoretic mobility. The newly identified variants showed apparently normal maturation, but variant R136Q, identified in a patient with atypical AD, showed slower migration of the immature band. Clathrin heavy chain (CHC) was used as a loading control. b and c Whole-cell lysate and cell surface biotinylation analysis for variants R136Q and R136W demonstrate significantly reduced overall expression for variant R136W and significantly reduced surface expression for both variants (* p < 0.05, *** p < 0.001, **** p < 0.0001 by ANOVA followed by Holm-Sidak post hoc test). CHC was used a loading control for the cell lysates and to confirm the lack of non-specific biotinylation of cytosolic proteins. Results were quantified from three independent experiments