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J Cell Biol. 2010 June 28; 189(7): 1054.
PMCID: PMC2894460
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Secret passage to the inner nuclear membrane

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A swollen nucleus lacking Nup188 and Nup93 (left) dwarfs a normal nucleus (right).

Proteins enter the inner nuclear membrane through a side door in the nuclear pore complex, Theerthagiri et al. report.

The double membrane that envelops the nucleus causes delivery problems for the cell. Newly made membrane-embedded proteins can travel directly to the outer nuclear membrane (ONM) because it connects to the endoplasmic reticulum. But how do such proteins reach the inner nuclear membrane (INM)? Researchers have suggested that the ONM and INM temporarily fuse to allow protein transfer or that vesicles ferry the proteins across the inter-membrane gap. Another possibility is that the proteins slip across via the nuclear pore complexes that span the two membranes.

Theerthagiri et al. found the latter case to be true using nuclei from Xenopus egg extracts lacking certain nucleoporins, or Nups. Nup93 and Nup188 belong to a complex that anchors the nuclear pore to both membranes, and the team showed that nuclei missing these pore components balloon to 4 or 5 times their normal volume. The nuclei enlarge because their INM accumulates more protein than normal.

Loss of the two Nups didn't affect transport through the main nuclear pore channel, but it sped up entry of the INM proteins, indicating that they use an alternative portal. The researchers think that INM proteins pass through accessory channels in the nuclear pore complex that flank the main entranceway. Nup93 and Nup188 could serve as gatekeepers for these side channels, opening them to allow certain molecules through. How the Nups determine which molecules to admit is still unclear.

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