title: TMEM120A and B: Nuclear Envelope Transmembrane Proteins Important for Adipocyte Differentiation.
abstract: Recent work indicates that the nuclear envelope is a major signaling node for the cell that can influence tissue differentiation processes. Here we present two nuclear envelope trans-membrane proteins TMEM120A and TMEM120B that are paralogs encoded by the Tmem120A and Tmem120B genes. The TMEM120 proteins are expressed preferentially in fat and both are induced during 3T3-L1 adipocyte differentiation. Knockdown of one or the other protein altered expression of several genes required for adipocyte differentiation, Gata3, Fasn, Glut4, while knockdown of both together additionally affected Pparg and Adipoq. The double knockdown also increased the strength of effects, reducing for example Glut4 levels by 95% compared to control 3T3-L1 cells upon pharmacologically induced differentiation. Accordingly, TMEM120A and B knockdown individually and together impacted on adipocyte differentiation/metabolism as measured by lipid accumulation through binding of Oil Red O and coherent anti-Stokes Raman scattering microscopy (CARS). The nuclear envelope is linked to several lipodystrophies through mutations in lamin A; however, lamin A is widely expressed. Thus it is possible that the TMEM120A and B fat-specific nuclear envelope transmembrane proteins may play a contributory role in the tissue-specific pathology of this disorder or in the wider problem of obesity.
authors.affiliation: Wellcome Trust Center for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Dzmitry G
authors.initials: DG
authors.lastname: Batrakou
authors.affiliation: Wellcome Trust Center for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Jose I
authors.initials: JI
authors.lastname: de Las Heras
authors.affiliation: Wellcome Trust Center for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Rafal
authors.initials: R
authors.lastname: Czapiewski
authors.affiliation: Institute for Materials and Processes, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Rabah
authors.initials: R
authors.lastname: Mouras
authors.affiliation: Wellcome Trust Center for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D051275:Glucose Transporter Type 4; D008565:Membrane Proteins; D047495:PPAR gamma; C495693:Slc2a4 protein, mouse