Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.

Autor: Wang L; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China.; Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland., Yang Z; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Satoshi F; Helsinki Institute of Life Science - Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Prasanna X; Department of Physics, University of Helsinki, Helsinki, Finland., Yan Z; Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland., Vihinen H; Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Chen Y; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Zhao Y; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., He X; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China.; School of Life Sciences, Guangxi Normal University, Guilin, China.; Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin, 541004, China., Bu Q; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Li H; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Zhao Y; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Jiang L; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Qin F; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Dai Y; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Zhang N; Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China., Qin M; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Kuang W; Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China., Zhao Y; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China., Jokitalo E; Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Vattulainen I; Department of Physics, University of Helsinki, Helsinki, Finland., Kajander T; Helsinki Institute of Life Science - Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Zhao H; Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland. hongxia.zhao@helsinki.fi.; School of Life Sciences, Guangxi Normal University, Guilin, China. hongxia.zhao@helsinki.fi.; Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin, 541004, China. hongxia.zhao@helsinki.fi., Cen X; Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, China. xbcen@scu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 23; Vol. 15 (1), pp. 6209. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1038/s41467-024-50565-w
Abstrakt: The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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