title: FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation.
abstract: Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173-220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120-140 are essential but not sufficient for LD enlargement, whereas amino acids 120-210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation.
authors.affiliation: Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Srikarthika
authors.initials: S
authors.lastname: Jambunathan
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Waheed
authors.initials: W
authors.lastname: Khan
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tamori
authors.forename: Vishwajeet
authors.initials: V
authors.lastname: Puri
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016000:Cluster Analysis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014280:Triglycerides; D049452:Green Fluorescent Proteins