@article{281e9a83a6df49919e6b8513b3233a3a,
title = "A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size",
abstract = "Lipid droplets (LDs) are the major fat storage organelles in eukaryotic cells, but how their size is regulatedis unknown. Using genetic screens in C.elegans for LD morphology defects in intestinal cells, we found that mutations in atlastin, a GTPase required for homotypic fusion of endoplasmic reticulum (ER) membranes, cause not only ER morphology defects, but also a reduction in LD size. Similar results were obtained after depletion of atlastin or expression of a dominant-negative mutant, whereas overexpression of atlastin had the opposite effect. Atlastin depletion in Drosophila fat bodies also reduced LD size and decreased triglycerides in whole animals, sensitizing them to starvation. In mammalian cells, co-overexpression of atlastin-1 and REEP1, a paralog of the ER tubule-shaping protein DP1/REEP5, generates large LDs. The effect of atlastin-1 on LD size correlates with its activity to promote membrane fusion invitro. Our results indicate that atlastin-mediated fusion of ER membranes is important for LD size regulation.",
author = "Klemm, {Robin W.} and Norton, {Justin P.} and Cole, {Ronald A.} and Li, {Chen S.} and Park, {Seong H.} and Crane, {Matthew M.} and Liying Li and Diana Jin and Alexandra Boye-Doe and Liu, {Tina Y.} and Yoko Shibata and Hang Lu and Rapoport, {Tom A.} and Farese, {Robert V.} and Craig Blackstone and Yi Guo and Mak, {Ho Yi}",
note = "Funding Information: We thank Sabrina Caldwell for the initial mapping of altn-1 alleles, and the Stowers Institute Microscopy Center for assistance with imaging. We thank the Mayo Clinic Microscopy and Cell Analysis Core Facility for assistance with TEM and CARS applications. We thank the Nikon Imaging Center at Harvard Medical School for help. This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH (C.B.), a Mayo Clinic New Investigator Startup Fund and Richard F. Emslander Career Development Award (Y.G.), the National Institutes of Health grants R01-GM099844 (R.V.F.), R01AG035317 (H.L.), R01GM088333 (H.L.), the National Science Foundation grant CBET 0954578 (H.L.), and the Stowers Institute for Medical Research (H.Y.M.). T.A.R. is a Howard Hughes Medical Institute investigator. Author contributions: Mak lab: Figures 1, 2, S1, and S2; Rapoport lab: Figures 4 (except C), S4; Guo and Farese labs: Figures 3 and S3; Blackstone lab: Figure 4C. Genetic screens were conducted in the Mak and Lu labs. R.W.K., T.A.R., Y.G., and H.Y.M. wrote the manuscript. ",
year = "2013",
month = may,
day = "30",
doi = "10.1016/j.celrep.2013.04.015",
language = "English (US)",
volume = "3",
pages = "1465--1475",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}