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- W3201130819 abstract "Clustered protocadherins (Pcdhs) are a large family of cadherin-like cell adhesion proteins that are central for neurite self-avoidance and neuronal connectivity in the brain. Their downstream nonreceptor tyrosine kinase Pyk2 (proline-rich tyrosine kinase 2, also known as Ptk2b, Cakb, Raftk, Fak2, and Cadtk) is predominantly expressed in the hippocampus. We constructed Pyk2-null mouse lines and found that these mutant mice showed enhancement in contextual fear memory, without significant change in auditory-cued and spatial-referenced learning and memory. In addition, by preparing Y402F mutant mice, we observed that Pyk2 suppressed contextual fear memory in an autophosphorylation-independent manner. Moreover, using high-throughput RNA sequencing, we found that immediate early genes, such as Npas4, cFos, Zif268/Egr1, Arc, and Nr4a1, were enhanced in Pyk2-null mice. We further showed that Pyk2 disruption affected pyramidal neuronal complexity and spine dynamics. Thus, we demonstrated that Pyk2 is a novel fear memory suppressor molecule and Pyk2-null mice provide a model for understanding fear-related disorders. These findings have interesting implications regarding dysregulation of the Pcdh‒Pyk2 axis in neuropsychiatric disorders." @default.
- W3201130819 created "2021-09-27" @default.
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- W3201130819 date "2021-09-16" @default.
- W3201130819 modified "2023-10-18" @default.
- W3201130819 title "Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner" @default.
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- W3201130819 doi "https://doi.org/10.1093/jmcb/mjab057" @default.
- W3201130819 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34529077" @default.
- W3201130819 hasPublicationYear "2021" @default.
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