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dc.contributor.authorKralt, Annemarie
dc.contributor.authorBasheer, Noorjahan Jagalur
dc.contributor.authorVan Den Boom, Vincent
dc.contributor.authorLokareddy, Ravi K.
dc.contributor.authorSteen, Anton
dc.contributor.authorCingolani, Gino
dc.contributor.authorFornerod, Maarten
dc.contributor.authorVeenhoff, Liesbeth M.
dc.identifier.citationKralt A, Basheer NJ, Van Den Boom V, Lokareddy R, Steen A, Cingolani G, Fornerod M, Veenhoff L (2015) 'Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins', Molecular Biology of the Cell, 26 (18), pp.3301-3312.en_US
dc.description.abstractEndoplasmic reticulum-synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to the inner nuclear membrane (INM). Although many membrane proteins pass the NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these proteins, a nuclear localization signal (NLS) and an intrinsically disordered linker encode the sorting signal for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC. Here we address whether a similar import mechanism applies in metazoans. We show that the (putative) NLSs of metazoan HsSun2, MmLem2, HsLBR, and HsLap2β are not sufficient to drive nuclear accumulation of a membrane protein in yeast, but the NLS from RnPom121 is. This NLS of Pom121 adapts a similar fold as the NLS of Heh2 when transport factor bound and rescues the subcellular localization and synthetic sickness of Heh2ΔNLS mutants. Consistent with the conservation of these NLSs, the NLS and linker of Heh2 support INM localization in HEK293T cells. The conserved features of the NLSs of ScHeh1, ScHeh2, and RnPom121 and the effective sorting of Heh2-derived reporters in human cells suggest that active import is conserved but confined to a small subset of INM proteins.en_US
dc.publisherAmerican Society for Cell Biologyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectnuclear membrane targeting sequencesen_US
dc.subjectSubject Categories::C700 Molecular Biology, Biophysics and Biochemistryen_US
dc.titleConservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteinsen_US
dc.contributor.departmentUniversity of Groningenen_US
dc.contributor.departmentErasmus Medical Center/Sophia Children’s Hospitalen_US
dc.contributor.departmentThomas Jefferson Universityen_US
dc.identifier.journalMolecular Biology of the Cellen_US
dc.description.notepublisher makes oa with cc licence after 2m embargo

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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International