A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane.
Integral membrane proteins of the inner nuclear membrane (INM) are inserted into the endoplasmic reticulum membrane during their biogenesis and are then targeted to their final destination. We have used human SUN2 to delineate features that are required for INM targeting and have identified multiple elements that collectively contribute to the efficient localization of SUN2 to the nuclear envelope (NE). One such targeting element is a classical nuclear localization signal (cNLS) present in the N-terminal, nucleoplasmic domain of SUN2. A second motif proximal to the cNLS is a cluster of arginines that serves coatomer-mediated retrieval of SUN2 from the Golgi. Unexpectedly, also the C-terminal, lumenal SUN domain of SUN2 supports NE localization, showing that targeting elements are not limited to cytoplasmic or transmembrane domains of INM proteins. Together, SUN2 represents the first mammalian INM protein relying on a functional cNLS, a Golgi retrieval signal and a perinuclear domain to mediate targeting to the INM.
Turgay
Yagmur
Y
Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
Ungricht
Rosemarie
R
Rothballer
Andrea
A
Kiss
Alexa
A
Csucs
Gabor
G
Horvath
Peter
P
Kutay
Ulrike
U
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D008565:Membrane Proteins; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; C413025:SUN2 protein, human