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

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

  • Nat Commun. 2024 Jul 23;15(1):6209. doi: 10.1038/s41467-024-50565-w.
Liang Wang # 1 2,  Ziyun Yang # 1,  Fudo Satoshi 3,  Xavier Prasanna 4,  Ziyi Yan 2,  Helena Vihinen 5,  Yaxing Chen 1,  Yue Zhao 1,  Xiumei He 1 6 7,  Qian Bu 1,  Hongchun Li 1,  Ying Zhao 1,  Linhong Jiang 1,  Feng Qin 1,  Yanping Dai 1,  Ni Zhang 8,  Meng Qin 1,  Weihong Kuang 8,  Yinglan Zhao 1,  Eija Jokitalo 5,  Ilpo Vattulainen 4,  Tommi Kajander 3,  Hongxia Zhao 9 10 11,  Xiaobo Cen 12
Affiliations

Affiliations

  • 1 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.
  • 2 Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland.
  • 3 Helsinki Institute of Life Science - Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • 4 Department of Physics, University of Helsinki, Helsinki, Finland.
  • 5 Helsinki Institute of Life Science (HiLIFE) - Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • 6 School of Life Sciences, Guangxi Normal University, Guilin, China.
  • 7 Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin, 541004, China.
  • 8 Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
  • 9 Faculty of Biological and Environmental Sciences, University of Helsinki, 00014, Helsinki, Finland. hongxia.zhao@helsinki.fi.
  • 10 School of Life Sciences, Guangxi Normal University, Guilin, China. hongxia.zhao@helsinki.fi.
  • 11 Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin, 541004, China. hongxia.zhao@helsinki.fi.
  • 12 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.
  • # Contributed equally.
PMID: 39043703 DOI: 10.1038/s41467-024-50565-w
Abstract

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.

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