Karyopherin-mediated import of integral inner nuclear membrane proteins

• Published in: Nature 2006-08, Vol.442 (7106), p.1003-1007
• Main Authors: KING, Megan C, LUSK, C. Patrick, BLOBEL, Günter
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Binding sites; Biological and medical sciences; Cell physiology; Cellular biology; Fundamental and applied biological sciences. Psychology; GTP Phosphohydrolases - metabolism; Karyopherins - metabolism; Membrane and intracellular transports; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Molecular and cellular biology; Nuclear Envelope - metabolism; Nuclear Localization Signals; Nuclear Pore - chemistry; Nuclear Pore - metabolism; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Protein Binding; Protein Transport; Proteins; ran GTP-Binding Protein - metabolism; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature05075

Targeting of newly synthesized integral membrane proteins to the appropriate cellular compartment is specified by discrete sequence elements, many of which have been well characterized. An understanding of the signals required to direct integral membrane proteins to the inner nuclear membrane (INM) remains a notable exception. Here we show that integral INM proteins possess basic sequence motifs that resemble 'classical' nuclear localization signals. These sequences can mediate direct binding to karyopherin-alpha and are essential for the passage of integral membrane proteins to the INM. Furthermore, karyopherin-alpha, karyopherin-beta1 and the Ran GTPase cycle are required for INM targeting, underscoring parallels between mechanisms governing the targeting of integral INM proteins and soluble nuclear transport. We also provide evidence that specific nuclear pore complex proteins contribute to this process, suggesting a role for signal-mediated alterations in the nuclear pore complex to allow for passage of INM proteins along the pore membrane.