| First Author | Zheng J | Year | 2022 |
| Journal | J Mol Cell Biol | Volume | 13 |
| Issue | 11 | Pages | 808-821 |
| PubMed ID | 34529077 | Mgi Jnum | J:326577 |
| Mgi Id | MGI:7314739 | Doi | 10.1093/jmcb/mjab057 |
| Citation | Zheng J, et al. (2022) Pyk2 suppresses contextual fear memory in an autophosphorylation-independent manner. J Mol Cell Biol 13(11):808-821 |
| abstractText | 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 PcdhPyk2 axis in neuropsychiatric disorders. |
