Role for formin-like 1-dependent acto-myosin assembly in lipid droplet dynamics and lipid storage

• Published in: Nature communications Vol. 8; no. 1; p. 14858
• Main Authors: Pfisterer, Simon G., Gateva, Gergana, Horvath, Peter, Pirhonen, Juho, Salo, Veijo T., Karhinen, Leena, Varjosalo, Markku, Ryhänen, Samppa J., Lappalainen, Pekka, Ikonen, Elina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.03.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/287/1182; 631/80/128/1276; 631/80/642; Acids; Actin Cytoskeleton - metabolism; Actomyosin; Animals; Cytoskeletal Proteins - metabolism; Enzymes; Formins; Hearing Loss, Sensorineural - metabolism; Humanities and Social Sciences; Humans; In Vitro Techniques; Intracellular Signaling Peptides and Proteins - metabolism; Lipid Droplets - metabolism; Lipid Metabolism; Lipids; Mice; Molecular Motor Proteins - metabolism; multidisciplinary; Myosin Heavy Chains - metabolism; Neutrophils - metabolism; Nonmuscle Myosin Type IIA - metabolism; Proteins; Proteome; RAW 264.7 Cells; Science; Science (multidisciplinary); Thrombocytopenia - congenital; Thrombocytopenia - metabolism; Triglycerides - metabolism; Finland
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14858

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. Lipid droplets (LDs) are cellular organelles dedicated to triacylglycerol storage that can undergo fusion and dissociation events. Here the authors show that formin-like 1-dependent acto-myosin assembly on LDs facilitates their dissociation and, as a consequence, affects hydrolysis and storage of triacylglycerols.