XB-ART-37067Mol Cell Biol. March 1, 2008; 28 (5): 1755-69.
Centrin 2 localizes to the vertebrate nuclear pore and plays a role in mRNA and protein export.
Centrins in vertebrates have traditionally been associated with microtubule-nucleating centers such as the centrosome. Unexpectedly, we found centrin 2 to associate biochemically with nucleoporins, including the Xenopus laevis Nup107-160 complex, a critical subunit of the vertebrate nuclear pore in interphase and of the kinetochores and spindle poles in mitosis. Immunofluorescence of Xenopus cells and in vitro reconstituted nuclei indeed revealed centrin 2 localized at the nuclear pores. Use of the mild detergent digitonin in immunofluorescence also allowed centrin 2 to be clearly visualized at the nuclear pores of human cells. Disruption of nuclear pores using RNA interference of the pore assembly protein ELYS/MEL-28 resulted in a specific decrease of centrin 2 at the nuclear rim of HeLa cells. Functionally, excess expression of either the N- or C-terminal calcium-binding domains of human centrin 2 caused a dominant-negative effect on both mRNA and protein export, leaving protein import intact. The mRNA effect mirrors that found for the Saccharomyes cerevisiae centrin Cdc31p at the yeast nuclear pore, a role until now thought to be unique to yeast. We conclude that in vertebrates, centrin 2 interacts with major subunits of the nuclear pore, exhibits nuclear pore localization, and plays a functional role in multiple nuclear export pathways.
PubMed ID: 18172010
PMC ID: PMC2258798
Article link: Mol Cell Biol.
Grant support: GM 68524 NIGMS NIH HHS , R01 GM-33279 NIGMS NIH HHS , R01 GM033279-24 NIGMS NIH HHS , R01 GM033279 NIGMS NIH HHS , K12 GM068524 NIGMS NIH HHS , R01 GM033279 NIGMS NIH HHS , R01 GM-33279 NIGMS NIH HHS , R01 GM033279-24 NIGMS NIH HHS , GM 68524 NIGMS NIH HHS
Genes referenced: mel nup107