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이계현Gyehyun Lee

서울대학교

Proc. Natl. Acad. Sci. USA, Mar 19 2024, 121 (12) | https://doi.org/10.1073/pnas.2313236121 Thermodynamic modulation of gephyrin condensation by inhibitory synapse components

Gyehyun Lee^a, Seungjoon Kim^b,c, Da- Eun Hwang^d, Yu- Gon Eom^d, Gyubin Jang^b,c, Hye Yoon Park^e,f, Jeong- Mo Choi^d,1, Jaewon Ko^b,c,1, and Yongdae Shin^a,g,1

^aDepartment of Mechanical Engineering, Seoul National University, Seoul 08826, Republic of Korea;

^bDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea;

^cCenter for Synapse Diversity and Specificity, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea;

^dDepartment of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Republic of Korea;

^eDepartment of Physics and Astronomy, Seoul National University, Seoul 08826, Republic of Korea;

^fDepartment of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455; and

^gInterdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea

¹To whom correspondence may be addressed. : Jeong- Mo Choi, Jaewon Ko, and Yongdae Shin

Abstract

Phase separation drives compartmentalization of intracellular contents into various biomolecular condensates. Individual condensate components are thought to differentially contribute to the organization and function of condensates. However, how intermolecular interactions among constituent biomolecules modulate the phase behaviors of multicomponent condensates remains unclear. Here, we used core components of the inhibitory postsynaptic density (iPSD) as a model system to quantitatively probe how the network of intra- and intermolecular interactions defines the composition and cellular distribution of biomolecular condensates. We found that oligomerization-driven phase separation of gephyrin, an iPSD-specific scaffold, is critically modulated by an intrinsically disordered linker region exhibiting minimal homotypic attractions. Other iPSD components, such as neurotransmitter receptors, differentially promote gephyrin condensation through distinct binding modes and affinities. We further demonstrated that the local accumulation of scaffold-binding proteins at the cell membrane promotes the nucleation of gephyrin condensates in neurons. These results suggest that in multicomponent systems, the extent of scaffold condensation can be fine-tuned by scaffold-binding factors, a potential regulatory mechanism for self-organized compartmentalization in cells.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-12)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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