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논문 기본 정보

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학술저널
저자정보
Cho Eunji (Seoul National University College of Medicine) Lee Sang Eun (Seoul National University College of Medicine) Lee Unghwi (Seoul National University College of Medicine) Goh Yuna (Seoul National University College of Medicine) Jeong Seonyoung (Seoul National University College of Medicine) Choi Junyoung (Ulsan National Institute of Science and Technology) Jeong Won-Ki (Korea University) Chang Sunghoe (Seoul National University College of Medicine)
저널정보
대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제55권
발행연도
2023.1
수록면
1 - 12 (12page)
DOI
10.1038/s12276-022-00918-6

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nArgBP2, a candidate gene for intellectual disability, is a postsynaptic protein critical for dendritic spine development and morphogenesis, and its knockdown (KD) in developing neurons severely impairs spine-bearing excitatory synapse formation. Surprisingly, nArgBP2 KD in mature neurons did not cause morphological defects in the existing spines at rest, raising questions of how it functions in mature neurons. We found that unlike its inaction at rest, nArgBP2 KD completely inhibited the enlargement of dendritic spines during chemically induced long-term potentiation (cLTP) in mature neurons. We further found that nArgBP2 forms condensates in dendritic spines and that these condensates are dispersed by cLTP, which spatiotemporally coincides with spine head enlargement. Condensates with CaMKII phosphorylation-deficient mutant or CaMKII inhibition are neither dispersed nor accompanied by spine enlargement during cLTP. We found that nArgBP2 condensates in spines exhibited liquid-like properties, and in heterologous and in vitro expression systems, nArgBP2 undergoes liquid-liquid phase separation via multivalent intermolecular interactions between SH3 domains and proline-rich domains. It also forms coacervates with CaMKIIα, which is rapidly dissembled by calcium/CaMKIIα-dependent phosphorylation. We further showed that the interaction between nArgBP2 and WAVE1 competes with nArgBP2 phase separation and that blocking the nArgBP2-WAVE1 interaction prevents spine enlargement during cLTP. Together, our results suggest that nArgBP2 at rest is confined to the condensates but is released by CaMKIIα-mediated phosphorylation during synaptic plasticity, which regulates its timely interaction with WAVE1 to induce spine head enlargement in mature neurons.

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