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Proc Natl Acad Sci USA 논문 게재 (06.20.2024)

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댓글 0건 조회 33회 작성일 2024-06-24 09:45

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DGIST 뇌과학과 엄지원 교수님 그룹과의 공동연구를 통해 보편적 시냅스 억제인자인 MDGA 단백질에 의한 다양한 시냅스 특성을 조절하는 분자기전을 규명한 연구결과를 PNAS 지에 게재하였습니다. 실험실에서는 김승준 박사 (박사과정 졸업생)와 장규빈 연구원 (석사과정 졸업생)이 공동1저자, 김현호 박사 (박사과정 졸업생), 임동석 학생 (석사과정), 한경아 연구교수 등이 공동저자로 본 연구에 참여하였습니다. 모두 축하드립니다. 


 Gyubin Jang, [...]Jaewon Ko

 

MDGA (MAM domain containing glycosylphosphatidylinositol anchor) family proteins were previously identified as synaptic suppressive factors. However, various genetic manipulations have yielded often irreconcilable results, precluding precise evaluation of MDGA functions. Here, we found that, in cultured hippocampal neurons, conditional deletion of MDGA1 and MDGA2 causes specific alterations in synapse numbers, basal synaptic transmission, and synaptic strength at GABAergic and glutamatergic synapses, respectively. Moreover, MDGA2 deletion enhanced both N-methyl-D-aspartate (NMDA) receptor- and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated postsynaptic responses. Strikingly, ablation of both MDGA1 and MDGA2 abolished the effect of deleting individual MDGAs that is abrogated by chronic blockade of synaptic activity. Molecular replacement experiments further showed that MDGA1 requires the meprin/A5 protein/PTPmu (MAM) domain, whereas MDGA2 acts via neuroligin-dependent and/or MAM domain-dependent pathways to regulate distinct postsynaptic properties. Together, our data demonstrate that MDGA paralogs act as unique negative regulators of activity-dependent postsynaptic organization at distinct synapse types, and cooperatively contribute to adjustment of excitation–inhibition balance.

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