Cell Biology

Little and Large

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Science  24 May 2013:
Vol. 340, Issue 6135, pp. 902
DOI: 10.1126/science.340.6135.902-b
CREDIT: C. SNOW ET AL., THE JOURNAL OF CELL BIOLOGY 201, 4 (6 MAY 2013) © 2013 THE ROCKEFELLER UNIVERSITY PRESS

The import of proteins into the nucleus occurs through pores in the nuclear envelope and depends on the Ran GTPase system. Previous work has shown that the nuclear import of the protein Tpr (translocated promoter region) is compromised in fibroblasts that express the Progerin protein associated with Hutchinson-Gilford progeria syndrome (HGPS) (below; see bottom row, purple). These findings were attributed to deficiencies in the Ran GTPase system, whereby Ran GTP accumulates in the nucleus to promote the release of nuclear import cargoes from their receptors. Following up on these findings, Snow et al. now show that, rather than a global reduction in nuclear import, the limitations on Tpr import reflect difficulties in the import of large protein cargoes into the nucleus. Tpr is a nucleoporin that forms a basketlike structure on the nuclear side of nuclear pores. Its import into the nucleus is particularly sensitive to the Ran gradient across the nuclear envelope. The extent to which problems with Tpr import or the import of other large protein cargoes contributes to the premature aging phenotypes observed in HGPS patients remains unclear.

J. Cell Biol. 10.1083/jcb.201212117 (2013).

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