title: Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus by membranes associated with a novel nuclear pore structure.
abstract: DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Goodwin
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Nasim
authors.initials: N
authors.lastname: Motamedi
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Lipovsky
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Busnadiego
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut, United States of America; Department of Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut, United States of America; Yale Cancer Center, New Haven, Connecticut, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D055032:Electron Microscope Tomography; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055785:Gene Knockdown Techniques; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism* / Q000648:ultrastructure*; D021381:Protein Transport
chemical_list: D015415:Biomarkers; C494649:DNAJB12 protein, human; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins
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