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Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation.
Roberts, Melissa A; Deol, Kirandeep K; Mathiowetz, Alyssa J; Lange, Mike; Leto, Dara E; Stevenson, Julian; Hashemi, Sayed Hadi; Morgens, David W; Easter, Emilee; Heydari, Kartoosh; Nalls, Mike A; Bassik, Michael C; Kampmann, Martin; Kopito, Ron R; Faghri, Faraz; Olzmann, James A.
Afiliação
  • Roberts MA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Deol KK; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Mathiowetz AJ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Lange M; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Leto DE; Department of Biology, Stanford University, Stanford, CA 94305, USA.
  • Stevenson J; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Hashemi SH; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
  • Morgens DW; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Easter E; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Heydari K; Cancer Research Laboratory FACS Core Facility, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Nalls MA; Data Tecnica International, LLC, Washington, DC, USA; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bassik MC; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Kampmann M; Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kopito RR; Department of Biology, Stanford University, Stanford, CA 94305, USA.
  • Faghri F; Data Tecnica International, LLC, Washington, DC, USA; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
  • Olzmann JA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: olzmann@ber
Dev Cell ; 58(18): 1782-1800.e10, 2023 09 25.
Article em En | MEDLINE | ID: mdl-37494933
ABSTRACT
Despite the key roles of perilipin-2 (PLIN2) in governing lipid droplet (LD) metabolism, the mechanisms that regulate PLIN2 levels remain incompletely understood. Here, we leverage a set of genome-edited human PLIN2 reporter cell lines in a series of CRISPR-Cas9 loss-of-function screens, identifying genetic modifiers that influence PLIN2 expression and post-translational stability under different metabolic conditions and in different cell types. These regulators include canonical genes that control lipid metabolism as well as genes involved in ubiquitination, transcription, and mitochondrial function. We further demonstrate a role for the E3 ligase MARCH6 in regulating triacylglycerol biosynthesis, thereby influencing LD abundance and PLIN2 stability. Finally, our CRISPR screens and several published screens provide the foundation for CRISPRlipid (http//crisprlipid.org), an online data commons for lipid-related functional genomics data. Our study identifies mechanisms of PLIN2 and LD regulation and provides an extensive resource for the exploration of LD biology and lipid metabolism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistemas CRISPR-Cas / Gotículas Lipídicas Limite: Humans Idioma: En Revista: Dev Cell Assunto da revista: EMBRIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sistemas CRISPR-Cas / Gotículas Lipídicas Limite: Humans Idioma: En Revista: Dev Cell Assunto da revista: EMBRIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos