TY - JOUR
T1 - Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation
AU - Eisenberg-Bord, Michal
AU - Mari, Muriel
AU - Weill, Uri
AU - Rosenfeld-Gur, Eden
AU - Moldavski, Ofer
AU - Castro, Ines G.
AU - Soni, Krishnakant G.
AU - Harpaz, Nofar
AU - Levine, Tim P.
AU - Futerman, Anthony H.
AU - Reggiori, Fulvio
AU - Bankaitis, Vytas A.
AU - Schuldiner, Maya
AU - Bohnert, Maria
N1 - We thank Chaim Kahana for helpful discussions; Pedro Carvalho for the Sei1 and Ldb16 antibodies; Jodi Nunnari, Naama Barkai, and Jeffrey Gerst for plasmids; Yoav Peleg from the Dana and Yossie Hollander Center for Structural Proteomics for generation of the LDO plasmids; Nir Cohen for help with analysis of microscopy data; and Meital Kupervaser for help with proteomic data analysis. Mass spectrometry was performed by the de Botton Institute for Protein Profiling, G-INCPM, Weizmann Institute of Science. Work in the Schuldiner Laboratory was supported by the Deutsche Forschungsgemeinschaft grant SFB 1190 and a grant from the Volkswagen Foundation (93091). M. Schuldiner is an incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. M. Eisenberg-Bord was supported by the Azrieli Foundation with an Azrieli Fellowship. F. Reggiori was supported by Swiss National Science Foundation Sinergia (CRSII3_154421) and ZonMw VICI (016.130.606) grants. K.G. Soni and V.A. Bankaitis were supported by the National Institutes of Health grant RO1 GM44530 and the Welch Foundation grant BE-0017. T.P. Levine was funded by the UK Biotechnology and Biological Sciences Research Council, project BB/M011801/1. M. Bohnert was supported by the European Commission Horizon 2020 research and innovation program under the Marie Sklodovska-Curie grant 705853. Author contributions: Conceptualization was performed by M. Eisenberg-Bord, M. Schuldiner, and M. Bohnert; the investigation was performed by M. Eisenberg-Bord., M. Mari, U. Weill, E. Rosenfeld-Gur, O. Moldavski, I.G. Castro, K.G. Soni, N. Harpaz, T.P. Levine, and M. Bohnert; visualization was by M. Eisenberg-Bord, M. Mari, T.P. Levine, and M. Bohnert; the paper was written by M. Schuldiner and M. Bohnert and was reviewed and edited by M. Eisenberg-Bord, M. Mari, U. Weill, O. Moldavski, I.G. Castro, T.P. Levine, F. Reggiori, V.A. Bankaitis, M. Schuldiner, and M. Bohnert: supervision was provided by A.H. Futerman, F. Reggiori, V.A. Bankaitis, M. Schuldiner, and M. Bohnert; and funding acquisition was by T.P. Levine, A.H. Futerman, F. Reggiori, V.A. Bankaitis, and M. Schuldiner.
PY - 2018
Y1 - 2018
N2 - Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus-vacuole junction contact site. In search for factors determining identity of these LDs, we screened ~6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.
AB - Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus-vacuole junction contact site. In search for factors determining identity of these LDs, we screened ~6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.
UR - http://www.scopus.com/inward/record.url?scp=85039864812&partnerID=8YFLogxK
U2 - 10.1083/jcb.201704122
DO - 10.1083/jcb.201704122
M3 - مقالة
C2 - 29187527
SN - 0021-9525
VL - 217
SP - 269
EP - 282
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -