Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins.

Authors

Annemarie Kralt, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen
Noorjahan B Jagalur, Departments of Biochemistry and Pediatric Oncology, Erasmus MC/Sophia
Vincent van den Boom, Department of Experimental Hematology, University Medical Center Groningen, University of Groningen
Ravi K Lokareddy, Department of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Anton Steen, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen
Gino Cingolani, Dept. of Biochemistry and Molecular Biology, Thomas Jefferson UniversityFollow
Maarten Fornerod, Departments of Biochemistry and Pediatric Oncology, Erasmus MC/Sophia
Liesbeth M Veenhoff, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen

Document Type

Article

Publication Date

9-15-2015

Comments

This article has been peer reviewed. It was published in: Molecular Biology of the Cell.

Volume 26, Issue 18, 15 September 2015, Pages 3301-3312.

The published version is available at DOI: 10.1091/mbc.E15-03-0184

Copyright © 2015 Kralt et al.

Abstract

Endoplasmic 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.

Recommended Citation

Kralt, Annemarie; Jagalur, Noorjahan B; van den Boom, Vincent; Lokareddy, Ravi K; Steen, Anton; Cingolani, Gino; Fornerod, Maarten; and Veenhoff, Liesbeth M, "Conservation of inner nuclear membrane targeting sequences in mammalian Pom121 and yeast Heh2 membrane proteins." (2015). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 90.
https://jdc.jefferson.edu/bmpfp/90

PubMed ID

26179916