title: F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from structure to human diseases.
abstract: Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. suxuan.liu@temple.edu.|Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. suxuan.liu@temple.edu.
authors.forename: Suxuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. xinyu.xiong@duke.edu.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. xianxianz2010@163.com.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. xfyang@temple.edu.|Center for Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. xfyang@temple.edu.|Center for Thrombosis Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. xfyang@temple.edu.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. hongw@temple.edu.|Center for Metabolic Disease Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. hongw@temple.edu.|Center for Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. hongw@temple.edu.|Center for Thrombosis Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA. hongw@temple.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051578:Proto-Oncogene Proteins c-fes / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; C406285:TRIP10 protein, human; C075637:amphiphysin; D051578:Proto-Oncogene Proteins c-fes