Resendes KK, et al. (2008) Centrin 2 Localizes to the Vertebrate Nuclear Pore and Plays a Role in mRNA and Protein Export. Mol Cell Biol 28(5):1755-1769
Abstract: 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 Nup107-160 complex, a critical subunit of the vertebrate nuclear pore in interphase and of kinetochores and spindle poles in mitosis. Immunofluorescence on Xenopus cells and in vitro reconstituted nuclei indeed revealed centrin 2 to be 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 RNAi 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 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.
|Status: Published||Type: Journal Article||PubMed ID: 18172010|
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