title: Role for formin-like 1-dependent acto-myosin assembly in lipid droplet dynamics and lipid storage.
abstract: Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs. FMNL1 is required for actin assembly on LDs in vitro and for NMIIa recruitment to LDs in cells. We propose a novel acto-myosin structure regulating lipid storage: FMNL1-dependent assembly of myosin II-functionalized actin filaments on LDs facilitates their dissociation, thereby affecting LD surface-to-volume ratio and enzyme accessibility to TGs. In neutrophilic leucocytes from MYH9-related disease patients NMIIa inclusions are accompanied by increased lipid storage in droplets, suggesting that NMIIa dysfunction may contribute to lipid imbalance in man.
authors.affiliation: Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.|Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Pfisterer
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
authors.forename: Gergana
authors.initials: G
authors.lastname: Gateva
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.|Synthetic and Systems Biology Unit, Hungarian Academy of Sciences, BRC, Szeged H-6726, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Horvath
authors.affiliation: Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.|Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Pirhonen
authors.affiliation: Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.|Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
authors.forename: Veijo T
authors.initials: VT
authors.lastname: Salo
authors.affiliation: Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Karhinen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Varjosalo
authors.affiliation: Division of Hematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki 00290, Finland.
authors.forename: Samppa J
authors.initials: SJ
authors.lastname: Ryhänen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.affiliation: Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.|Minerva Foundation Institute for Medical Research, Helsinki 00290, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Ikonen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000205:Actomyosin; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000080865:Formins; D006319:Hearing Loss, Sensorineural / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D020543:Proteome; D000067996:RAW 264.7 Cells; D013921:Thrombocytopenia / Q000151:congenital* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C476204:FMNL1 protein, human; C413382:Fmnl1 protein, mouse; D000080865:Formins; D047908:Intracellular Signaling Peptides and Proteins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C525088:Myh9 protein, mouse; D020543:Proteome; D014280:Triglycerides; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains