Nature 442, 1003-1007 (31 August 2006) | doi:10.1038/nature05075; Received 8 June 2006; Accepted 11 July 2006; Published online 23 August 2006

Karyopherin-mediated import of integral inner nuclear membrane proteins

Megan C. King1,2, C. Lusk1,2 and Günter Blobel1

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.

  1. Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
  2. *These authors contributed equally to this work

Correspondence to: Megan C. King1,2C. Lusk1,2 Correspondence and requests for materials should be addressed to M.C.K. (Email: or C.P.L. (Email:


These links to content published by NPG are automatically generated.


Highway to the inner nuclear membrane: rules for the road

Nature Reviews Molecular Cell Biology Perspective (01 May 2007)

See all 24 matches for Reviews


Cell biology Taking a turn into the nucleus

Nature News and Views (31 Aug 2006)

A sorting importin on Sec61

Nature Structural & Molecular Biology News and Views (01 Jun 2006)

See all 8 matches for News And Views

Extra navigation