(a) Co-IP of GFP-PKARIIβ with wild-type, R1441C, G2019S, and G2835 LRRK2 from transfected cells (a). (b) The relative binding affinity of GFP-PKARIIβ with LRRK2 proteins (n=3). t(4)=3.070, 0.2735, and 2.016. (c) Co-IP of GST-LRRK2 and GST-R1441C with MBP-PKARIIβ recombinant proteins. (d) GFP-PKARIIβ and mCherry signals in the spines and dendrites of 15DIV cultured hippocampal neurons. Scale bar: 5μm. (e,f) Quantification of GFP-PKARIIβ signal in the spines (f, n=70–75 spines from six neurons per genotype), and the spine size (g, n=60 spines from four neurons per genotype)..t=2.552 and 2,145, respectively. (h–k) The pS3 versus total cofilin (h,i) and pS845 versus total GluR1 (j,k) in the forebrain homogenate of P15 LRRK2+/+, LRRK2+/R1441C and LRRK2R1441C/R1441C mice. n=3 per genotype. t(4)=1.935 and 3.182 in (h), 3.918 and 5.191 in (j). (l–n) The pS845 versus total GluR1 in the striatum of P21 LRRK2+/+ (n=8), LRRK2+/R1441C (n=4), and LRRK2R1441C/R1441C (n=4) mice (l,m), and 18-month-old LRRK2+/+ (n=4) and LRRK2RC/RC (n=4) mice (n). t(10)=0.3237, 0.7222, 2.865, and 3.283 in (m). t(6)=3.303 and 4.083 in (m). (o–q) The ambulatory (o), fine (p), and rearing movement (q) of P21 LRRK2+/+, LRRK2−/−, and LRRK2+/RC mice after treated with saline (n=16, 37, and 10) or SKF81297 at 2 (n=21, 28, and 11) and 10mg per kg bodyweight (n=27, 28, and 10). Data represent mean ± SEM. Unpaired test (b,e,f,h,j,l,m) and two-way ANOVA plus Bonferroni post-tests (m–q) were used.