| First Author | Stepan J | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 10 | Pages | 111766 |
| PubMed ID | 36476872 | Mgi Jnum | J:332146 |
| Mgi Id | MGI:7410743 | Doi | 10.1016/j.celrep.2022.111766 |
| Citation | Stepan J, et al. (2022) Hippo-released WWC1 facilitates AMPA receptor regulatory complexes for hippocampal learning. Cell Rep 41(10):111766 |
| abstractText | Learning and memory rely on changes in postsynaptic glutamergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor (AMPAR) number, spatial organization, and function. The Hippo pathway component WW and C2 domain-containing protein 1 (WWC1) regulates AMPAR surface expression and impacts on memory performance. However, synaptic binding partners of WWC1 and its hierarchical position in AMPAR complexes are largely unclear. Using cell-surface proteomics in hippocampal tissue of Wwc1-deficient mice and by generating a hippocampus-specific interactome, we show that WWC1 is a major regulatory platform in AMPAR signaling networks. Under basal conditions, the Hippo pathway members WWC1 and large tumor-suppressor kinase (LATS) are associated, which might prevent WWC1 effects on synaptic proteins. Reduction of WWC1/LATS binding through a point mutation at WWC1 elevates the abundance of WWC1 in AMPAR complexes and improves hippocampal-dependent learning and memory. Thus, uncoupling of WWC1 from the Hippo pathway to AMPAR-regulatory complexes provides an innovative strategy to enhance synaptic transmission. |
