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Published Erratum
. 2025 Jun 10;122(23):e2511044122.
doi: 10.1073/pnas.2511044122. Epub 2025 May 30.

Correction for Yin et al., Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

No authors listed
Published Erratum

Correction for Yin et al., Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

No authors listed. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Fig. 1.
Fig. 1.
Tau accumulation in the hippocampal CA3 region impairs learning and memory. (A) The representative immunofluorescence imaging of the hippocampus and the enlarged CA3 subset after infusion of AAV-eGFP-hTau for 6 wk. [Scale bars: 200 μm (Left) and 20 μm (Right).] (B) Expression of hTau in hippocampal CA3 was confirmed by Western blotting using human tau-specific antibody HT7. (C) The escape latency to find the hidden platform in MWM during the 6-d learning process. (D–F) The escape latency to find the hidden platform, the target platform crossings, and the time spent in the target quadrant measured on day 8 by removing the platform. (G) After a 1-wk rest, fear conditioning was used to measure the contextual memory: the mice were exposed to foot shocks for 2 s (0.8 mA) followed by an auditory cue. After 24 h, the mice were put into the same training chamber without shocks and the auditory cue, and the total freezing time in 3 min was recorded with a video camera. (H) Two hours later, the freezing time in 3 min was measured again by putting the mice back into the same chamber with the auditory cue for 30 s. Data were expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. vector (Vec).
Fig. 3.
Fig. 3.
Overexpression of hTau inactivates nuclear CREB with up-regulation of CaN and inhibition of CaMKIV. (A and B) Hippocampal neurons (7 div) were infected with lenti-mCherry-hTau or the vector and cultured for 5 more days, then the cell lysates and the nuclear fraction were prepared for Western blotting of total and the Ser133-phosphorylated levels of CREB. (C) The representative immunofluorescence imaging showing reduced nuclear staining of pCREB (red) in neurons with overexpression of hTau probed by HT7 (green). (Scale bar, 5 μm.) (D–F) The protein levels of total and the pCaMKIV, total CaN-A and CaN-B, and the cleaved CaN-A (cCaN-A) in cell lysates and the nuclear fraction detected by Western blotting. (G and H) The reduced pCaMKIV (red) and increased CaN-B (red) in the nuclear fraction of the primary hippocampal neurons detected by immunofluorescent staining. (Scale bar, 5 μm.) (I and J) The increased protein levels of CaN-A and cCaN-A, CaN-B, and reduced pCaMKIV and pCREB detected in nuclear fraction of the hippocampal CA3 subset after infusion of AAV-eGFP-hTau for 6 wk. (K) The CaN activity in primary cultured hippocampal neurons (PCHNs) and mouse hippocampus CA3 (MHCA3) detected by using the activity assay kit. (L–N) Total PP2A, the demethylated PP2A at Leu309 (deML309-PP2A), and the phosphorylated PP2A at tyrosine-307 (pY307-PP2A), total ERK, and pERK in cell lysates, and the level of PP1 catalytic subunit in the nuclear fraction measured by Western blotting. Lamin B and DAPI were used, respectively, as nuclear markers. Data were expressed as mean ± SEM, *P < 0.05, **P < 0.01 vs. Vec.
Fig. 4.
Fig. 4.
Inhibition of CaN attenuates the hTau-induced CREB dephosphorylation independent of its effects on CaMKIV inhibition. (A–D) The primary hippocampal neurons (7 div) were infected with lenti-mCherry-hTau or the vector, after being cultured for 5 more days, the neurons were treated with 1 μM FK506 or 50 nM CsA for 12 h, then the levels pS133-CREB and pS196-CaMKIV were measured by Western blotting. (E and F) N2A cells, cotransfected with hTau plus CaMKBP4 or CaMKIVK75E plasmids for 48 h, were treated with 1 μM FK506 for 12 h, and then the phosphorylation level of CREB in the nuclear fraction was measured by Western blotting. Data were expressed as mean ± SEM, *P < 0.05 vs. Vec; #P < 0.05 vs. hTau; and &P < 0.05 vs. hTau plus CaMKBP4; $P < 0.05 vs. hTau plus CaMKIVK75E.
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